Elizabeth Mechcatie

Pioglitazone, a thiazolidinedione used to reduce insulin resistance in patients with type 2 diabetes, was well tolerated in a pilot study of nondiabetic patients with probable Alzheimer’s disease, providing support for continuing studies of this class of drugs in early stages of Alzheimer’s, according to a report published online on Sept. 13 in the Archives of Neurology.

Safety was the primary objective of the study, and while no effects of treatment on clinical efficacy, a secondary outcome, were observed, the authors concluded that “disappointing results of treatment trials based on the amyloid hypothesis, and the reasonable degree of safety identified in this trial, suggest that exploratory studies of thiazolidinediones remain warranted.” The lead author was Dr. David Geldmacher, of the University of Virginia, Charlottesville, one of the two study sites.

In the double-blind, placebo-controlled study, 29 patients who met the criteria for probable Alzheimer’s disease (AD) were randomized to receive pioglitazone, titrated to 45 mg/day, or placebo, plus 100 IU vitamin E daily, for 18 months, between 2001 and 2004. They continued treatment with cholinesterase inhibitors; 20%-27% of the patients also received memantine, once it became available.

Pioglitazone, marketed as Actos as a treatment for type 2 diabetes, is a potent inhibitor of peroxisome proliferator–activated receptor gamma (PPARg), a nuclear receptor that that regulates glucose and lipid metabolism, which are abnormal in AD. This is a “potential therapeutic target for the treatment of AD,” because PPARg activation “robustly suppresses inflammation as well as expression of cytokines and other inflammatory mediators associated with activated microglia,” they said, noting that that, “a local microglia-mediated inflammatory response centers on the amyloid plaques in the AD brain.”

They referred to some evidence that rosiglitazone, another thiazolidinedione, had “limited efficacy,” in patients with early AD, but the results were mixed. This was the first study of pioglitazone in patients with AD, they said.

In the study, almost 29% of those on pioglitazone developed peripheral edema, a known adverse effect associated with pioglitazone, compared with none of the patients on placebo. But otherwise, there were no serious adverse events, and the drug was well tolerated, with “no pattern of effect on blood glucose levels, hemoglobin A1c levels, or other blood chemistry or hematologic measures,” they said (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.229]).

As expected, because of the small size of the study, “no significant effect of treatment was observed on any clinical outcome measures,” which included measures of cognition and activities of daily living, the authors said.

The authors recommended that future studies of these agents should focus on earlier stages of disease and “be augmented by biomarkers, such as nuclear imaging techniques, to measure changes in microglial activation associated with treatment.” They noted that these studies will need to closely monitor patients for peripheral edema and other cardiovascular morbidities.

The study was supported by the National Institute of Aging. Pioglitazone manufacturer Takeda Pharmaceuticals North America provided the pioglitazone and placebo tablets free of charge but had no other role in the conduct or analysis of the study. Two of the four authors have received consulting fees from Takeda and consulting fees and research support from GlaxoSmithKline. One of the study sites, Case Western Reserve University, Cleveland, has a patent for the use of pioglitazone in the treatment of AD and other CNS disorders.

Pioglitazone, a thiazolidinedione used to reduce insulin resistance in patients with type 2 diabetes, was well tolerated in a pilot study of nondiabetic patients with probable Alzheimer’s disease, providing support for continuing studies of this class of drugs in early stages of Alzheimer’s, according to a report published online on Sept. 13 in the Archives of Neurology.

Safety was the primary objective of the study, and while no effects of treatment on clinical efficacy, a secondary outcome, were observed, the authors concluded that “disappointing results of treatment trials based on the amyloid hypothesis, and the reasonable degree of safety identified in this trial, suggest that exploratory studies of thiazolidinediones remain warranted.” The lead author was Dr. David Geldmacher, of the University of Virginia, Charlottesville, one of the two study sites.

In the double-blind, placebo-controlled study, 29 patients who met the criteria for probable Alzheimer’s disease (AD) were randomized to receive pioglitazone, titrated to 45 mg/day, or placebo, plus 100 IU vitamin E daily, for 18 months, between 2001 and 2004. They continued treatment with cholinesterase inhibitors; 20%-27% of the patients also received memantine, once it became available.

Pioglitazone, marketed as Actos as a treatment for type 2 diabetes, is a potent inhibitor of peroxisome proliferator–activated receptor gamma (PPARg), a nuclear receptor that that regulates glucose and lipid metabolism, which are abnormal in AD. This is a “potential therapeutic target for the treatment of AD,” because PPARg activation “robustly suppresses inflammation as well as expression of cytokines and other inflammatory mediators associated with activated microglia,” they said, noting that that, “a local microglia-mediated inflammatory response centers on the amyloid plaques in the AD brain.”

They referred to some evidence that rosiglitazone, another thiazolidinedione, had “limited efficacy,” in patients with early AD, but the results were mixed. This was the first study of pioglitazone in patients with AD, they said.

In the study, almost 29% of those on pioglitazone developed peripheral edema, a known adverse effect associated with pioglitazone, compared with none of the patients on placebo. But otherwise, there were no serious adverse events, and the drug was well tolerated, with “no pattern of effect on blood glucose levels, hemoglobin A1c levels, or other blood chemistry or hematologic measures,” they said (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.229]).

As expected, because of the small size of the study, “no significant effect of treatment was observed on any clinical outcome measures,” which included measures of cognition and activities of daily living, the authors said.

The authors recommended that future studies of these agents should focus on earlier stages of disease and “be augmented by biomarkers, such as nuclear imaging techniques, to measure changes in microglial activation associated with treatment.” They noted that these studies will need to closely monitor patients for peripheral edema and other cardiovascular morbidities.

The study was supported by the National Institute of Aging. Pioglitazone manufacturer Takeda Pharmaceuticals North America provided the pioglitazone and placebo tablets free of charge but had no other role in the conduct or analysis of the study. Two of the four authors have received consulting fees from Takeda and consulting fees and research support from GlaxoSmithKline. One of the study sites, Case Western Reserve University, Cleveland, has a patent for the use of pioglitazone in the treatment of AD and other CNS disorders.

Pioglitazone, a thiazolidinedione used to reduce insulin resistance in patients with type 2 diabetes, was well tolerated in a pilot study of nondiabetic patients with probable Alzheimer’s disease, providing support for continuing studies of this class of drugs in early stages of Alzheimer’s, according to a report published online on Sept. 13 in the Archives of Neurology.

Safety was the primary objective of the study, and while no effects of treatment on clinical efficacy, a secondary outcome, were observed, the authors concluded that “disappointing results of treatment trials based on the amyloid hypothesis, and the reasonable degree of safety identified in this trial, suggest that exploratory studies of thiazolidinediones remain warranted.” The lead author was Dr. David Geldmacher, of the University of Virginia, Charlottesville, one of the two study sites.

In the double-blind, placebo-controlled study, 29 patients who met the criteria for probable Alzheimer’s disease (AD) were randomized to receive pioglitazone, titrated to 45 mg/day, or placebo, plus 100 IU vitamin E daily, for 18 months, between 2001 and 2004. They continued treatment with cholinesterase inhibitors; 20%-27% of the patients also received memantine, once it became available.

Pioglitazone, marketed as Actos as a treatment for type 2 diabetes, is a potent inhibitor of peroxisome proliferator–activated receptor gamma (PPARg), a nuclear receptor that that regulates glucose and lipid metabolism, which are abnormal in AD. This is a “potential therapeutic target for the treatment of AD,” because PPARg activation “robustly suppresses inflammation as well as expression of cytokines and other inflammatory mediators associated with activated microglia,” they said, noting that that, “a local microglia-mediated inflammatory response centers on the amyloid plaques in the AD brain.”

They referred to some evidence that rosiglitazone, another thiazolidinedione, had “limited efficacy,” in patients with early AD, but the results were mixed. This was the first study of pioglitazone in patients with AD, they said.

In the study, almost 29% of those on pioglitazone developed peripheral edema, a known adverse effect associated with pioglitazone, compared with none of the patients on placebo. But otherwise, there were no serious adverse events, and the drug was well tolerated, with “no pattern of effect on blood glucose levels, hemoglobin A1c levels, or other blood chemistry or hematologic measures,” they said (Arch. Neurol. 2010 Sept. 13 [doi:10.1001/archneurol.2010.229]).

As expected, because of the small size of the study, “no significant effect of treatment was observed on any clinical outcome measures,” which included measures of cognition and activities of daily living, the authors said.

The authors recommended that future studies of these agents should focus on earlier stages of disease and “be augmented by biomarkers, such as nuclear imaging techniques, to measure changes in microglial activation associated with treatment.” They noted that these studies will need to closely monitor patients for peripheral edema and other cardiovascular morbidities.

The study was supported by the National Institute of Aging. Pioglitazone manufacturer Takeda Pharmaceuticals North America provided the pioglitazone and placebo tablets free of charge but had no other role in the conduct or analysis of the study. Two of the four authors have received consulting fees from Takeda and consulting fees and research support from GlaxoSmithKline. One of the study sites, Case Western Reserve University, Cleveland, has a patent for the use of pioglitazone in the treatment of AD and other CNS disorders.

A drug that has been used to treat nerve gas and other types of pesticide and chemical poisoning in children off-label for years is now approved for pediatric use, the Food and Drug Administration announced on Sept. 9.

The drug, pralidoxime chloride, available as Protopam Chloride in the United States, was approved in 1964, as a treatment for poisoning caused by organophosphate pesticides and chemicals, such as nerve agents, in adults. It is now available in an intramuscular formulation in addition to the previously available intravenous formulation. Protopam Chloride, manufactured by Baxter Healthcare Corp., works by acting as an antidote “by slowing the attachment of the chemical to nerve endings,” according to the FDA statement announcing the approval.

Because it is now approved for pediatric use, the label will include dosing information in children, which will provide health care professionals with information on “how to use this drug safely and effectively,” Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

Using intravenous drugs in children, especially in emergency situations, can be difficult, so “having the new option of intramuscular injection might help health care professionals use this medicine quickly and accurately,” Dr. Dianne Murphy, director of the FDA’s Office of Pediatric Therapeutics, pointed out in the statement.

Blurred vision, double vision, dizziness, headache, drowsiness, nausea, difficulty breathing, increased heart rate, and increased blood pressure are among the adverse reactions associated with the drug in adults and children, according to the FDA.

Symptoms associated with poisoning with organophosphate pesticides or chemicals can range from mild symptoms, such as a runny nose or vomiting, to serious symptoms that include difficult breathing, weakness, and convulsions, according to the FDA.

A drug that has been used to treat nerve gas and other types of pesticide and chemical poisoning in children off-label for years is now approved for pediatric use, the Food and Drug Administration announced on Sept. 9.

The drug, pralidoxime chloride, available as Protopam Chloride in the United States, was approved in 1964, as a treatment for poisoning caused by organophosphate pesticides and chemicals, such as nerve agents, in adults. It is now available in an intramuscular formulation in addition to the previously available intravenous formulation. Protopam Chloride, manufactured by Baxter Healthcare Corp., works by acting as an antidote “by slowing the attachment of the chemical to nerve endings,” according to the FDA statement announcing the approval.

Because it is now approved for pediatric use, the label will include dosing information in children, which will provide health care professionals with information on “how to use this drug safely and effectively,” Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

Using intravenous drugs in children, especially in emergency situations, can be difficult, so “having the new option of intramuscular injection might help health care professionals use this medicine quickly and accurately,” Dr. Dianne Murphy, director of the FDA’s Office of Pediatric Therapeutics, pointed out in the statement.

Blurred vision, double vision, dizziness, headache, drowsiness, nausea, difficulty breathing, increased heart rate, and increased blood pressure are among the adverse reactions associated with the drug in adults and children, according to the FDA.

Symptoms associated with poisoning with organophosphate pesticides or chemicals can range from mild symptoms, such as a runny nose or vomiting, to serious symptoms that include difficult breathing, weakness, and convulsions, according to the FDA.

A drug that has been used to treat nerve gas and other types of pesticide and chemical poisoning in children off-label for years is now approved for pediatric use, the Food and Drug Administration announced on Sept. 9.

The drug, pralidoxime chloride, available as Protopam Chloride in the United States, was approved in 1964, as a treatment for poisoning caused by organophosphate pesticides and chemicals, such as nerve agents, in adults. It is now available in an intramuscular formulation in addition to the previously available intravenous formulation. Protopam Chloride, manufactured by Baxter Healthcare Corp., works by acting as an antidote “by slowing the attachment of the chemical to nerve endings,” according to the FDA statement announcing the approval.

Because it is now approved for pediatric use, the label will include dosing information in children, which will provide health care professionals with information on “how to use this drug safely and effectively,” Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

Using intravenous drugs in children, especially in emergency situations, can be difficult, so “having the new option of intramuscular injection might help health care professionals use this medicine quickly and accurately,” Dr. Dianne Murphy, director of the FDA’s Office of Pediatric Therapeutics, pointed out in the statement.

Blurred vision, double vision, dizziness, headache, drowsiness, nausea, difficulty breathing, increased heart rate, and increased blood pressure are among the adverse reactions associated with the drug in adults and children, according to the FDA.

Symptoms associated with poisoning with organophosphate pesticides or chemicals can range from mild symptoms, such as a runny nose or vomiting, to serious symptoms that include difficult breathing, weakness, and convulsions, according to the FDA.

GAITHERSBURG, Md. – Food and Drug Administration's Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA).

Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration's Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA).

Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration's Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA).

Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – Food and Drug Administration’s Anti-Infective Drugs Advisory Committee on Sept. 7 voted 18-0 that ceftaroline has been shown to be safe and effective for treating complicated skin and skin structure infections, based on the results of two clinical trials.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam of the cephalosporin class, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. Ceftaroline exhibits broad-spectrum antibacterial activity against important skin pathogens, according to its manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc.

Cerexa has proposed that ceftaroline fosamil for injection be approved for the treatment of adults with complicated skin and skin structure infections (cSSSI), caused by susceptible isolates of gram-positive and gram-negative microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA). Earlier in the day, the same panel also unanimously agreed that the drug had been shown to be safe and effective in treating community-acquired bacterial pneumonia (CABP). But the proposed CABP indication did not include infections caused by MRSA. These infections were not studied in the CABP trials, a fact that several panelists emphasized should be explained in the drug’s label, to avoid confusion among clinicians.

The proposed cSSSI dose is 600 mg administered intravenously every 12 hours for 5-14 days, with a lower dose for people with moderate to severe renal impairment.

In two identically designed multinational, double-blind, noninferiority phase III studies of almost 1,400 patients with a variety of cSSSI, patients were randomized to treatment with ceftaroline monotherapy (at the proposed dose for 5-14 days), or vancomycin (1 g IV every 12 hours) plus aztreonam (1 g IV every 12 hours) for 5-14 days. Criteria for enrollment included the need to be hospitalized or treated in an emergency department or urgent care setting, and the expectation that at least 5 days of intravenous antimicrobial treatment would be required. About 78% of patients had S. aureus infections; of those, 45%-49% had methicillin-sensitive S. aureus (MSSA) infections and about 29%-33% had MRSA infections.

The primary end point was the clinical cure rate (total resolution of signs and symptoms or improvement to the extent that no more antibiotics were needed) 8-15 days after the end of therapy. Among those who had received at least one dose in the two studies, the clinical cure rate was about 86% in both groups. The clinical cure rate for infections caused by S. aureus, the most common pathogen, was almost 89% among those on ceftaroline, compared with 87% of those on the comparator therapy. For methicillin-sensitive S. aureus (MSSA) infections, the cure rate was 90% in both the ceftaroline-treated patients and among those on the comparator therapy. For MRSA infections, the clinical cure rate was nearly 87% among those on ceftaroline, compared with 82% of those on vancomycin plus aztreonam.

The most common adverse events in both treatment groups were nausea, headache, and diarrhea. The rate of serious adverse events was low in both groups, at about 4%, as were the rates of adverse events resulting in discontinuation of the drug of study (3% among those on ceftaroline and almost 5% among those on the comparator treatment).

One issue raised by panelists was why a weight-based dosing regimen for vancomycin had not been used in the study.

The company is planning to conduct several pediatric studies of the drug.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting. Occasionally, the FDA grants a waiver to a panelist with a conflict of interest, but not at this meeting.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

GAITHERSBURG, Md. – A Food and Drug Administration advisory panel voted 21 to 0 that the antimicrobial drug ceftaroline fosamil had been shown to be safe and effective for treating community-acquired bacterial pneumonia, based on the result of two clinical trials.

At a meeting of the FDA’s Anti-Infective Drugs Advisory Committee Sept. 7, panelists were enthusiastic about the drug, but had some concerns, including the lack of data in patients with methicillin-resistant Staphylococcus aureus (MRSA) since it’s likely the drug would be used to treat such infections. Another concern was the generalizability of the data, since the studies were done largely in Eastern European patients.

The manufacturer, Cerexa Inc., a subsidiary of Forest Laboratories Inc., has proposed that ceftaroline fosamil be approved for the treatment of adults with community-acquired bacterial pneumonia (CABP) or complicated skin and skin structure infections (cSSSI). The panel will discuss and vote on the cSSSI indication during the afternoon session of the meeting.

Ceftaroline, the active metabolite of ceftaroline fosamil, is a beta-lactam in the cephalosporin class of antimicrobials, with antibacterial activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria, which are associated with skin and respiratory infections. The proposed dose for treating CABP is 600 mg administered intravenously every 12 hours, for 5-7 days, with a reduced dose for patients with moderate renal impairment.

In two international nearly identical phase III noninferiority studies of 1,240 patients with moderate to severe CABP, the effectiveness of treatment with ceftaroline at the proposed dose for 5-7 days was similar to treatment with the comparator, ceftriaxone (1 g IV every 24 hours). Effectiveness was based on the primary end point, clinical response at test of cure (TOC), 8-15 days after completing treatment. Clinical cure was defined as total resolution of all signs and symptoms of pneumonia or improvements to the extent that further antimicrobial treatment was not recommended. This end point was met by 84% and 81% of those treated with ceftaroline in the two studies, compared with 78% and 76% among those on the comparator, respectively. These results met the 10% noninferiority margin.

The safety profile of ceftaroline was similar to that expected for other cephalosporins, according to the company and FDA reviewers. The most common adverse reactions among those on ceftaroline were GI-related, such as diarrhea or nausea, followed by nervous system complaints such as headaches. The panelists also agreed that the safety profile was comparable to what would be expected with cephalosporins.

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline "should be considered" when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen "most clearly" in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non-ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is "often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection," the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline “should be considered” when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen “most clearly” in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non–ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is “often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection,” the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline “should be considered” when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen “most clearly” in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non–ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is “often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection,” the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Alternatives to tigecycline “should be considered” when treating patients with serious infections because the intravenous antibiotic has been associated with an increased mortality rate in this population, according to a safety alert issued by the Food and Drug Administration on Sept. 1.

In a pooled analysis of 13 clinical trials of patients with different types of infections, treatment with tigecycline (Tygacil) was associated with increased mortality when compared with other antibiotics, according to the FDA statement. The increased risk was seen “most clearly” in patients with hospital-acquired pneumonia (HAP), and particularly ventilator-associated pneumonia (VAP); tigecycline is not approved for either condition. Among patients with HAP, 14.1% of those on tigecycline died, compared with 12.2% of those treated with other antibiotics. In the subgroup of patients with VAP, 19.1% of those treated with tigecycline died, compared with 12.3% of those treated with other antibiotics.

But there was no difference in the mortality rates among the rest of the patients with HAP, who were classified as having non–ventilator associated pneumonia, which was 12.2% among both those treated with tigecycline and among those treated with other antibiotics.

Mortality was also increased in patients who were treated with tigecycline for complicated skin and skin structure infections (cSSSI) and complicated intra-abdominal infections (cIAI) – both approved indications – and diabetic foot infections – an unapproved indication – when compared with other antibiotics: Among those with cSSSI, 1.4% of those treated with tigecycline died, compared with 0.7% of those who received other antibiotics. The mortality rate among those with cIAI treated with tigecycline was 3%, compared with 2.2% of those treated with other antibiotics.

The mortality in patients with diabetic foot infections was 1.3% among those who were treated with tigecycline, compared with 0.6% of those treated with other antibiotics.

Tigecycline, a tetracycline antibacterial, also is approved for the treatment of community-acquired pneumonia. Mortality rates were similar among those patients with CAP treated with tigecycline and those treated with other antibiotics.

The cause of the excess deaths in these studies is “often uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection,” the statement said.

A letter to the manufacturer, Pfizer Pharmaceuticals Inc., posted on the FDA’s Web site in July also notes that in some studies, QT prolongation was more common among patients in the tigecycline arm and requests that Pfizer conduct a QTc study of patients treated with tigecycline.

Serious adverse events associated with tigecycline should be reported to the FDA’s MedWatch program or at 800-332-1088.

Long-term use of the weight loss drug sibutramine was not associated with an increased risk of death; however, the drug was associated with a significantly increased risk of nonfatal myocardial infarctions and strokes among overweight and obese people with preexisting cardiovascular conditions, based on data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial.

The rate of nonfatal MIs associated with sibutramine was increased by 28% and the rate of nonfatal stroke was increased by 36%, compared with placebo in the randomized, double-blind multicenter study, which was conducted in Europe, Central and South America, and Australia from January 2003 through March 2009 (N. Engl. J. Med. 2010 Sept. 1;363:905-17).

Abbott Laboratories, which has marketed the drug in the United States as Meridia since its approval in 1997, funded SCOUT. Sibutramine is a norepinephrine and serotonin reuptake inhibitor that induces satiety and is known to be associated with modest increases in blood pressure and resting pulse rates.

The results indicate sibutramine “should continue to be excluded from use in patients with pre-existing cardiovascular disease,” concluded Dr. W. Philip T. James of the London School of Hygiene and Tropical Medicine, and the other authors of the study.

In an accompanying editorial, titled “Sibutramine – Another Flawed Diet Pill,” Dr. Gregory Curfman and his coauthors wrote that this conclusion is “based on a narrow interpretation of the SCOUT data, in which only the patients with preexisting cardiovascular disease had an increase in the risk of new cardiovascular events.” While this was a “defensible interpretation” of the data, they pointed out that marketing of sibutramine in the European Union was withdrawn in January 2010 based on early results of SCOUT (N. Engl. J. Med. 2010 Sept. 1;363:972-4).

The SCOUT results will be reviewed at a September 15 meeting of the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Panel.

While noting the need for safe and effective weight loss medications, the authors of the editorial stated: “Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome cardiovascular risk profile, and a plausible mechanism to explain the cardiovascular risk, it is difficult to discern a credible rationale for keeping this medication on the market.”

The study compared the primary outcome – nonfatal MI, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death – in about 9,000 obese or overweight men and women. All were randomized to receive placebo or 10 mg/day of sibutramine after both groups had received sibutramine as part of a weight management program for 6 weeks. Study participants were aged 51-88 years (mean age, 63 years) and had preexisting cardiovascular disease, type 2 diabetes, or both. During the initial 6-week phase, the mean weight loss was 2.6 kg. Those who stayed on sibutramine lost a mean of another 1.7 kg after 1 year (for a total of 4.3 kg, or 9.5 pounds), while those on placebo had a mean weight gain of 0.7 kg.

Over a mean 3.4 years of treatment, the rate of the primary outcome was 11.4% among those on sibutramine, compared with 10% among those on placebo, an increased risk of 16% that was statistically significant. There were no significant differences in the cardiovascular death rates and the rate of death from any cause (a secondary outcome) among those on sibutramine, compared with those on placebo.

The nonfatal MI rate in the sibutramine-treated patients was 4.1%, compared with 3.2% in the placebo group, and the rate of nonfatal stroke was 2.6% among those on sibutramine, compared with 1.9% among those on placebo. The rate of resuscitation after cardiac arrest was 0.2% or less in the two groups.

The risk of nonfatal events was increased among sibutramine users with preexisting cardiovascular disease and with cardiovascular disease and type 2 diabetes. Risk was not increased among those with type 2 diabetes alone. The increase in nonfatal events might be caused by the “recognized effect of increased blood pressure on cardiovascular outcomes, and the combined peripheral and central sympathomimetic effects” of the drug, the authors wrote.

During the initial 6 weeks, when all patients were receiving sibutramine, systolic blood pressure dropped by a mean of 4.7 mm Hg and diastolic blood pressure dropped by a mean of 1.7 mm Hg. These values remained below the initial measurements in both groups during the remainder of the study, but were “consistently higher” among those on sibutramine, with mean differences of 1 mm Hg-2 mm Hg.

The mean pulse rate among those on sibutramine was also “consistently higher” than among those on placebo, with mean differences of 2.2 to 3.7 beats per minute.

The SCOUT authors cite several limitations of the study. The enrollment of mostly high-risk patients meant that most of the study patients did not meet the treatment criteria in the drug’s label, which warns against the use of sibutramine in patients with preexisting cardiovascular disease.

The editorialists observed that after 1 year, those on sibutramine gained back about 0.5 kg, so had a net weight loss of about 4 kg – almost 9 pounds – from an average of 96 kg (211 pounds) at baseline. “Thus, in exchange for an average weight loss of less than 4 kg, a subject had a 1 in 70 chance (or a 1 in 52 chance for those with known cardiovascular disease) of having a myocardial infarction or stroke – an unattractive benefit-to-risk ratio,” they wrote.

The study was funded by sibutramine manufacturer Abbott Laboratories. Author disclosures included having received lecture fees and travel reimbursement from Abbott. Abbott employees were among the authors of the study. The lead author has served on advisory boards for and has received travel reimbursements from GlaxoSmithKline, the manufacturer of orlistat, another weight loss drug.

The coauthors of the editorial were Stephen Morrissey, Ph.D., and Dr. Jeffrey Drazen. The authors of the editorial declared no conflicts of interest.

Long-term use of the weight loss drug sibutramine was not associated with an increased risk of death; however, the drug was associated with a significantly increased risk of nonfatal myocardial infarctions and strokes among overweight and obese people with preexisting cardiovascular conditions, based on data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial.

The rate of nonfatal MIs associated with sibutramine was increased by 28% and the rate of nonfatal stroke was increased by 36%, compared with placebo in the randomized, double-blind multicenter study, which was conducted in Europe, Central and South America, and Australia from January 2003 through March 2009 (N. Engl. J. Med. 2010 Sept. 1;363:905-17).

Abbott Laboratories, which has marketed the drug in the United States as Meridia since its approval in 1997, funded SCOUT. Sibutramine is a norepinephrine and serotonin reuptake inhibitor that induces satiety and is known to be associated with modest increases in blood pressure and resting pulse rates.

The results indicate sibutramine “should continue to be excluded from use in patients with pre-existing cardiovascular disease,” concluded Dr. W. Philip T. James of the London School of Hygiene and Tropical Medicine, and the other authors of the study.

In an accompanying editorial, titled “Sibutramine – Another Flawed Diet Pill,” Dr. Gregory Curfman and his coauthors wrote that this conclusion is “based on a narrow interpretation of the SCOUT data, in which only the patients with preexisting cardiovascular disease had an increase in the risk of new cardiovascular events.” While this was a “defensible interpretation” of the data, they pointed out that marketing of sibutramine in the European Union was withdrawn in January 2010 based on early results of SCOUT (N. Engl. J. Med. 2010 Sept. 1;363:972-4).

The SCOUT results will be reviewed at a September 15 meeting of the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Panel.

While noting the need for safe and effective weight loss medications, the authors of the editorial stated: “Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome cardiovascular risk profile, and a plausible mechanism to explain the cardiovascular risk, it is difficult to discern a credible rationale for keeping this medication on the market.”

The study compared the primary outcome – nonfatal MI, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death – in about 9,000 obese or overweight men and women. All were randomized to receive placebo or 10 mg/day of sibutramine after both groups had received sibutramine as part of a weight management program for 6 weeks. Study participants were aged 51-88 years (mean age, 63 years) and had preexisting cardiovascular disease, type 2 diabetes, or both. During the initial 6-week phase, the mean weight loss was 2.6 kg. Those who stayed on sibutramine lost a mean of another 1.7 kg after 1 year (for a total of 4.3 kg, or 9.5 pounds), while those on placebo had a mean weight gain of 0.7 kg.

Over a mean 3.4 years of treatment, the rate of the primary outcome was 11.4% among those on sibutramine, compared with 10% among those on placebo, an increased risk of 16% that was statistically significant. There were no significant differences in the cardiovascular death rates and the rate of death from any cause (a secondary outcome) among those on sibutramine, compared with those on placebo.

The nonfatal MI rate in the sibutramine-treated patients was 4.1%, compared with 3.2% in the placebo group, and the rate of nonfatal stroke was 2.6% among those on sibutramine, compared with 1.9% among those on placebo. The rate of resuscitation after cardiac arrest was 0.2% or less in the two groups.

The risk of nonfatal events was increased among sibutramine users with preexisting cardiovascular disease and with cardiovascular disease and type 2 diabetes. Risk was not increased among those with type 2 diabetes alone. The increase in nonfatal events might be caused by the “recognized effect of increased blood pressure on cardiovascular outcomes, and the combined peripheral and central sympathomimetic effects” of the drug, the authors wrote.

During the initial 6 weeks, when all patients were receiving sibutramine, systolic blood pressure dropped by a mean of 4.7 mm Hg and diastolic blood pressure dropped by a mean of 1.7 mm Hg. These values remained below the initial measurements in both groups during the remainder of the study, but were “consistently higher” among those on sibutramine, with mean differences of 1 mm Hg-2 mm Hg.

The mean pulse rate among those on sibutramine was also “consistently higher” than among those on placebo, with mean differences of 2.2 to 3.7 beats per minute.

The SCOUT authors cite several limitations of the study. The enrollment of mostly high-risk patients meant that most of the study patients did not meet the treatment criteria in the drug’s label, which warns against the use of sibutramine in patients with preexisting cardiovascular disease.

The editorialists observed that after 1 year, those on sibutramine gained back about 0.5 kg, so had a net weight loss of about 4 kg – almost 9 pounds – from an average of 96 kg (211 pounds) at baseline. “Thus, in exchange for an average weight loss of less than 4 kg, a subject had a 1 in 70 chance (or a 1 in 52 chance for those with known cardiovascular disease) of having a myocardial infarction or stroke – an unattractive benefit-to-risk ratio,” they wrote.

The study was funded by sibutramine manufacturer Abbott Laboratories. Author disclosures included having received lecture fees and travel reimbursement from Abbott. Abbott employees were among the authors of the study. The lead author has served on advisory boards for and has received travel reimbursements from GlaxoSmithKline, the manufacturer of orlistat, another weight loss drug.

The coauthors of the editorial were Stephen Morrissey, Ph.D., and Dr. Jeffrey Drazen. The authors of the editorial declared no conflicts of interest.

Long-term use of the weight loss drug sibutramine was not associated with an increased risk of death; however, the drug was associated with a significantly increased risk of nonfatal myocardial infarctions and strokes among overweight and obese people with preexisting cardiovascular conditions, based on data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial.

The rate of nonfatal MIs associated with sibutramine was increased by 28% and the rate of nonfatal stroke was increased by 36%, compared with placebo in the randomized, double-blind multicenter study, which was conducted in Europe, Central and South America, and Australia from January 2003 through March 2009 (N. Engl. J. Med. 2010 Sept. 1;363:905-17).

Abbott Laboratories, which has marketed the drug in the United States as Meridia since its approval in 1997, funded SCOUT. Sibutramine is a norepinephrine and serotonin reuptake inhibitor that induces satiety and is known to be associated with modest increases in blood pressure and resting pulse rates.

The results indicate sibutramine “should continue to be excluded from use in patients with pre-existing cardiovascular disease,” concluded Dr. W. Philip T. James of the London School of Hygiene and Tropical Medicine, and the other authors of the study.

In an accompanying editorial, titled “Sibutramine – Another Flawed Diet Pill,” Dr. Gregory Curfman and his coauthors wrote that this conclusion is “based on a narrow interpretation of the SCOUT data, in which only the patients with preexisting cardiovascular disease had an increase in the risk of new cardiovascular events.” While this was a “defensible interpretation” of the data, they pointed out that marketing of sibutramine in the European Union was withdrawn in January 2010 based on early results of SCOUT (N. Engl. J. Med. 2010 Sept. 1;363:972-4).

The SCOUT results will be reviewed at a September 15 meeting of the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Panel.

While noting the need for safe and effective weight loss medications, the authors of the editorial stated: “Given that sibutramine has minimal efficacy for weight loss, no apparent benefit for clinical outcomes, a worrisome cardiovascular risk profile, and a plausible mechanism to explain the cardiovascular risk, it is difficult to discern a credible rationale for keeping this medication on the market.”

The study compared the primary outcome – nonfatal MI, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death – in about 9,000 obese or overweight men and women. All were randomized to receive placebo or 10 mg/day of sibutramine after both groups had received sibutramine as part of a weight management program for 6 weeks. Study participants were aged 51-88 years (mean age, 63 years) and had preexisting cardiovascular disease, type 2 diabetes, or both. During the initial 6-week phase, the mean weight loss was 2.6 kg. Those who stayed on sibutramine lost a mean of another 1.7 kg after 1 year (for a total of 4.3 kg, or 9.5 pounds), while those on placebo had a mean weight gain of 0.7 kg.

Over a mean 3.4 years of treatment, the rate of the primary outcome was 11.4% among those on sibutramine, compared with 10% among those on placebo, an increased risk of 16% that was statistically significant. There were no significant differences in the cardiovascular death rates and the rate of death from any cause (a secondary outcome) among those on sibutramine, compared with those on placebo.

The nonfatal MI rate in the sibutramine-treated patients was 4.1%, compared with 3.2% in the placebo group, and the rate of nonfatal stroke was 2.6% among those on sibutramine, compared with 1.9% among those on placebo. The rate of resuscitation after cardiac arrest was 0.2% or less in the two groups.

The risk of nonfatal events was increased among sibutramine users with preexisting cardiovascular disease and with cardiovascular disease and type 2 diabetes. Risk was not increased among those with type 2 diabetes alone. The increase in nonfatal events might be caused by the “recognized effect of increased blood pressure on cardiovascular outcomes, and the combined peripheral and central sympathomimetic effects” of the drug, the authors wrote.

During the initial 6 weeks, when all patients were receiving sibutramine, systolic blood pressure dropped by a mean of 4.7 mm Hg and diastolic blood pressure dropped by a mean of 1.7 mm Hg. These values remained below the initial measurements in both groups during the remainder of the study, but were “consistently higher” among those on sibutramine, with mean differences of 1 mm Hg-2 mm Hg.

The mean pulse rate among those on sibutramine was also “consistently higher” than among those on placebo, with mean differences of 2.2 to 3.7 beats per minute.

The SCOUT authors cite several limitations of the study. The enrollment of mostly high-risk patients meant that most of the study patients did not meet the treatment criteria in the drug’s label, which warns against the use of sibutramine in patients with preexisting cardiovascular disease.

The editorialists observed that after 1 year, those on sibutramine gained back about 0.5 kg, so had a net weight loss of about 4 kg – almost 9 pounds – from an average of 96 kg (211 pounds) at baseline. “Thus, in exchange for an average weight loss of less than 4 kg, a subject had a 1 in 70 chance (or a 1 in 52 chance for those with known cardiovascular disease) of having a myocardial infarction or stroke – an unattractive benefit-to-risk ratio,” they wrote.

The study was funded by sibutramine manufacturer Abbott Laboratories. Author disclosures included having received lecture fees and travel reimbursement from Abbott. Abbott employees were among the authors of the study. The lead author has served on advisory boards for and has received travel reimbursements from GlaxoSmithKline, the manufacturer of orlistat, another weight loss drug.

The coauthors of the editorial were Stephen Morrissey, Ph.D., and Dr. Jeffrey Drazen. The authors of the editorial declared no conflicts of interest.