Elizabeth Mechcatie

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

ADELPHI, Md. – The majority of a Food and Drug Administration advisory committee on Oct. 18 did not recommend changes in the way darbepoetin alfa is currently dosed for treating anemia in patients with chronic renal failure who are not on dialysis, based on the results of the TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study.

Darbepoetin alfa, an erythropoiesis-stimulating agent (ESA) marketed as Aranesp by Amgen Inc., approved in 2001, is indicated for treating anemia associated with chronic renal failure, in patients who are or are not on dialysis. Darbepoetin is similar to epotin alfa (approved in 1989 and marketed as Epogen and as Procrit), but has a longer half life. (Amgen manufactures Aranesp and Epogen, and Epogen is licensed to Johnson and Johnson.) In 2007, a warning about a greater risk of death and serious CV events associated with targeting higher hemoglobin levels with ESAs, compared with targeting lower levels, was added to the drugs’ labeling.

At the meeting, the FDA’s Cardiovascular and Renal Drugs Advisory Committee was asked to review data from the TREAT study of mostly female patients in their late 60s, with type 2 diabetes and chronic renal failure, who were not on dialysis, to evaluate whether targeting a hemoglobin level of 13 g/dL would reduce the risk of death, cardiovascular and renal outcomes, when compared to the control group of patients. No benefit on these outcomes was seen, although anemia was corrected. Those in the control group were given rescue therapy with darbepoetin once a month when hemoglobin dropped to below 9 g/dL, and treatment was stopped when hemoglobin increased to 9 g/dL or more.

Moreover, the rate of stroke was higher among those in the treatment group overall, compared with those in the control group (4% vs. 2%) and among those with a previous history of stroke, the rate of stroke was threefold higher in the treatment group (12% vs. 4%). Among the patients with a history of malignancy at baseline, the rate of death from malignancies during the study (but not necessarily related to the previous malignancy) was higher among those in the treatment group.

In the control group, the median hemoglobin level achieved was 10.6 g/dL and two-thirds of patients did not receive a blood transfusion, 54% did not require any rescue treatment, and 45% did not need a transfusion or rescue treatment.

But the panel voted 9 to 5 with 3 abstentions, against recommending that the regimen used in the TREAT control group be adopted as the dose for this group of patients. Those voting against recommending a change cited an inadequate amount of data and evidence to support a change, as well as concerns that some patients would suffer with the symptoms of low hemoglobin levels and not meet criteria for treatment.

A warning about the increased risk of stroke was added to the label of all ESAs in 2009. Most of the panel voted against recommending that darbepoetin should be avoided for all patients with chronic kidney disease who have a history of a stroke regardless of whether they were on dialysis. However, several voting no objected to the inclusion of patients with chronic kidney disease who were on dialysis in the FDA’s question, who were not in the TREAT trial. Panelists strongly recommended that patients who are treated with darbepoetin be provided with an adequate informed consent that fully explains the increased risk of stroke.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of possible conflicts of interest related to the topic of the meeting; in some cases, they receive a waiver, but not at this meeting.

An injectable formulation of adrenocorticotropic hormone, used off-label since the late 1950s to treat infantile spasms, has been formally approved for this indication.

The manufacturer, Questcor Pharmaceuticals Inc., announced on Oct. 15 that the Food and Drug Administration had approved H.P. Acthar gel, the trade name for repository corticotropin injection, for treating infantile spasms (IS) in infants and children younger than 2 years. IS are a rare, severe form of epilepsy that affects about 2,000 children in the United States every year, according to the company.

Acthar gel, approved by the FDA in 1952, has been used to treat IS for more than 50 years, and is recommended by the American Academy of Neurology and the Child Neurology Society as a treatment for IS. It was previously approved for various indications, including acute multiple sclerosis exacerbations and nephrotic syndrome. Acthar gel is a purified preparation of adrenocorticotropic hormone (ACTH), obtained from the pituitary glands of pigs.

At a meeting in May, in near unanimous votes, an FDA advisory panel agreed that there was enough evidence indicating that Acthar gel was effective and safe for this indication.

Questcor, which acquired the drug in 2001, has not conducted new studies of the drug but reanalyzed data from three small, published randomized controlled studies. To evaluate efficacy, these analyses used the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response). In the main study, published in 1996, 13 of the 15 (87%) infants treated with Acthar gel had an overall response, compared with 4 of the 14 (29%) treated with prednisone, a significant difference.

The most common side effects of Acthar are well-recognized steroid side effects, such as irritability, a cushingoid appearance (if used long enough), infections, and hypertension, but based on more than 50 years of experience, no unexpected side effects have emerged, company officials said at the advisory panel meeting.

During the open public hearing portion of the meeting, parents of children who had been treated with Acthar gel, as well as several adults who had been successfully treated for IS as infants, testified about the beneficial effect of the treatment. (Many of those testifying had their trips paid for by the company.)

Also testifying was Dr. Mary Andriola, a pediatric neurologist at the State University of New York, Stony Brook, who testified that she has used ACTH to treat IS since she started medical school in 1963. She said that she teaches residents and fellows to use ACTH so that they know how to use it, despite difficulties in the past obtaining the drug.

The only other FDA-approved treatment for IS is vigabatrin (Sabril), approved in 2009. Prednisone is also used off-label to treat IS. Acthar gel is not approved in any other country.

An injectable formulation of adrenocorticotropic hormone, used off-label since the late 1950s to treat infantile spasms, has been formally approved for this indication.

The manufacturer, Questcor Pharmaceuticals Inc., announced on Oct. 15 that the Food and Drug Administration had approved H.P. Acthar gel, the trade name for repository corticotropin injection, for treating infantile spasms (IS) in infants and children younger than 2 years. IS are a rare, severe form of epilepsy that affects about 2,000 children in the United States every year, according to the company.

Acthar gel, approved by the FDA in 1952, has been used to treat IS for more than 50 years, and is recommended by the American Academy of Neurology and the Child Neurology Society as a treatment for IS. It was previously approved for various indications, including acute multiple sclerosis exacerbations and nephrotic syndrome. Acthar gel is a purified preparation of adrenocorticotropic hormone (ACTH), obtained from the pituitary glands of pigs.

At a meeting in May, in near unanimous votes, an FDA advisory panel agreed that there was enough evidence indicating that Acthar gel was effective and safe for this indication.

Questcor, which acquired the drug in 2001, has not conducted new studies of the drug but reanalyzed data from three small, published randomized controlled studies. To evaluate efficacy, these analyses used the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response). In the main study, published in 1996, 13 of the 15 (87%) infants treated with Acthar gel had an overall response, compared with 4 of the 14 (29%) treated with prednisone, a significant difference.

The most common side effects of Acthar are well-recognized steroid side effects, such as irritability, a cushingoid appearance (if used long enough), infections, and hypertension, but based on more than 50 years of experience, no unexpected side effects have emerged, company officials said at the advisory panel meeting.

During the open public hearing portion of the meeting, parents of children who had been treated with Acthar gel, as well as several adults who had been successfully treated for IS as infants, testified about the beneficial effect of the treatment. (Many of those testifying had their trips paid for by the company.)

Also testifying was Dr. Mary Andriola, a pediatric neurologist at the State University of New York, Stony Brook, who testified that she has used ACTH to treat IS since she started medical school in 1963. She said that she teaches residents and fellows to use ACTH so that they know how to use it, despite difficulties in the past obtaining the drug.

The only other FDA-approved treatment for IS is vigabatrin (Sabril), approved in 2009. Prednisone is also used off-label to treat IS. Acthar gel is not approved in any other country.

An injectable formulation of adrenocorticotropic hormone, used off-label since the late 1950s to treat infantile spasms, has been formally approved for this indication.

The manufacturer, Questcor Pharmaceuticals Inc., announced on Oct. 15 that the Food and Drug Administration had approved H.P. Acthar gel, the trade name for repository corticotropin injection, for treating infantile spasms (IS) in infants and children younger than 2 years. IS are a rare, severe form of epilepsy that affects about 2,000 children in the United States every year, according to the company.

Acthar gel, approved by the FDA in 1952, has been used to treat IS for more than 50 years, and is recommended by the American Academy of Neurology and the Child Neurology Society as a treatment for IS. It was previously approved for various indications, including acute multiple sclerosis exacerbations and nephrotic syndrome. Acthar gel is a purified preparation of adrenocorticotropic hormone (ACTH), obtained from the pituitary glands of pigs.

At a meeting in May, in near unanimous votes, an FDA advisory panel agreed that there was enough evidence indicating that Acthar gel was effective and safe for this indication.

Questcor, which acquired the drug in 2001, has not conducted new studies of the drug but reanalyzed data from three small, published randomized controlled studies. To evaluate efficacy, these analyses used the end points of complete cessation of spasms and resolution of hypsarrhythmia on a prolonged video EEG (overall response). In the main study, published in 1996, 13 of the 15 (87%) infants treated with Acthar gel had an overall response, compared with 4 of the 14 (29%) treated with prednisone, a significant difference.

The most common side effects of Acthar are well-recognized steroid side effects, such as irritability, a cushingoid appearance (if used long enough), infections, and hypertension, but based on more than 50 years of experience, no unexpected side effects have emerged, company officials said at the advisory panel meeting.

During the open public hearing portion of the meeting, parents of children who had been treated with Acthar gel, as well as several adults who had been successfully treated for IS as infants, testified about the beneficial effect of the treatment. (Many of those testifying had their trips paid for by the company.)

Also testifying was Dr. Mary Andriola, a pediatric neurologist at the State University of New York, Stony Brook, who testified that she has used ACTH to treat IS since she started medical school in 1963. She said that she teaches residents and fellows to use ACTH so that they know how to use it, despite difficulties in the past obtaining the drug.

The only other FDA-approved treatment for IS is vigabatrin (Sabril), approved in 2009. Prednisone is also used off-label to treat IS. Acthar gel is not approved in any other country.

Long-term treatment with bisphosphonates may be related to an increased risk of atypical femur fractures in patients, who may experience weeks or even months of pain before fracture diagnosis, according to the final report issued by a task force convened by the American Society of Bone and Mineral Research.

The society created the international, multidisciplinary task force to address reports of “atypical fractures of the subtrochanteric region of the hip and the femoral shaft” in patients on long-term bisphosphonate therapy. A statement issued by the society announcing the release of the report referred to it as “the most comprehensive scientific report to date” on this issue. The task force based its report on findings from a review of published and unpublished data, interviews with scientists at companies that manufacture these drugs, and Food and Drug Administration data.

The review included an analysis of 310 published case reports of patients (aged 36-92 years) with atypical subtrochanteric and femoral shaft fractures. Of these patients, 291 (94%) had been treated with bisphosphonates, mostly for osteoporosis. The median duration of treatment was 7 years, and most were treated for more than 5 years, according to the report, which points out that these fractures are rare, accounting for less than 1% of the overall rate of hip and femur fractures (J. Bone Miner. Res. 2010 Sept. 14 [doi:10.1002/jbmr.253]).

More than half of the patients with such femur fractures had experienced a prodrome of pain in the groin or thigh for weeks or months, and fractures were bilateral in more than 25% of the patients.

“We are concerned that there may be a relationship between these fractures and long-term bisphosphonate use and, although the risk is low, we want to make sure that people know about the warning signs,” the task force cochair and lead author of the report, Dr. Elizabeth Shane, said in the ASBMR statement. “Health professionals should know the warning signs of atypical femur fractures, and regularly ask patients on these drugs about groin or thigh pain,” added Dr. Shane, professor of medicine at Columbia University in New York.

She also recommended that every year, clinicians evaluate whether bisphosphonate therapy is appropriate for patients on these drugs, and that the drugs “be reserved” for patients with Paget's disease, patients with osteoporosis who are at high risk of fractures, and patients with certain cancers, she added.

In the statement, Dr. Shane said that for the “vast majority of patients with osteoporosis, these drugs are an important weapon against fractures and their benefits far outweigh the risks.”

The ASBMR task force recommendations include establishing an international registry of patients with these fractures, increasing research to determine whether bisphosphonates are the cause, and improving the labeling of these products so that health care professionals and patients are more aware of the potential for these fractures and the associated symptoms.

A statement issued by the FDA said the agency “recommends that health care professionals be aware of the possible risk of unusual femur fractures in patients taking bisphosphonates. Patients should talk to their health care professional if they develop new thigh or groin pain so that they may be evaluated to rule out a femur fracture.”

Dr. Shane and other members of the task force disclosed relationships with manufacturers of bisphosphonates.

The task force report is available at www.jbmr.org/details/journalArticle/843323/Atypical_subtrochanteric_and_diaphyseal_femoral_fractures_Report_of_a_task_force.htmlwww.fda.gov/medwatch

This anterior-posterior radiograph of the left femur demonstrates a substantially transverse femoral fracture and associated diffuse periosteal new bone formation (black arrow) and focal cortical thickening (white arrow), consistent with atypical femoral shaft fracture.

Source Courtesy American Society for Bone and Mineral Research

Long-term treatment with bisphosphonates may be related to an increased risk of atypical femur fractures in patients, who may experience weeks or even months of pain before fracture diagnosis, according to the final report issued by a task force convened by the American Society of Bone and Mineral Research.

The society created the international, multidisciplinary task force to address reports of “atypical fractures of the subtrochanteric region of the hip and the femoral shaft” in patients on long-term bisphosphonate therapy. A statement issued by the society announcing the release of the report referred to it as “the most comprehensive scientific report to date” on this issue. The task force based its report on findings from a review of published and unpublished data, interviews with scientists at companies that manufacture these drugs, and Food and Drug Administration data.

The review included an analysis of 310 published case reports of patients (aged 36-92 years) with atypical subtrochanteric and femoral shaft fractures. Of these patients, 291 (94%) had been treated with bisphosphonates, mostly for osteoporosis. The median duration of treatment was 7 years, and most were treated for more than 5 years, according to the report, which points out that these fractures are rare, accounting for less than 1% of the overall rate of hip and femur fractures (J. Bone Miner. Res. 2010 Sept. 14 [doi:10.1002/jbmr.253]).

More than half of the patients with such femur fractures had experienced a prodrome of pain in the groin or thigh for weeks or months, and fractures were bilateral in more than 25% of the patients.

“We are concerned that there may be a relationship between these fractures and long-term bisphosphonate use and, although the risk is low, we want to make sure that people know about the warning signs,” the task force cochair and lead author of the report, Dr. Elizabeth Shane, said in the ASBMR statement. “Health professionals should know the warning signs of atypical femur fractures, and regularly ask patients on these drugs about groin or thigh pain,” added Dr. Shane, professor of medicine at Columbia University in New York.

She also recommended that every year, clinicians evaluate whether bisphosphonate therapy is appropriate for patients on these drugs, and that the drugs “be reserved” for patients with Paget's disease, patients with osteoporosis who are at high risk of fractures, and patients with certain cancers, she added.

In the statement, Dr. Shane said that for the “vast majority of patients with osteoporosis, these drugs are an important weapon against fractures and their benefits far outweigh the risks.”

The ASBMR task force recommendations include establishing an international registry of patients with these fractures, increasing research to determine whether bisphosphonates are the cause, and improving the labeling of these products so that health care professionals and patients are more aware of the potential for these fractures and the associated symptoms.

A statement issued by the FDA said the agency “recommends that health care professionals be aware of the possible risk of unusual femur fractures in patients taking bisphosphonates. Patients should talk to their health care professional if they develop new thigh or groin pain so that they may be evaluated to rule out a femur fracture.”

Dr. Shane and other members of the task force disclosed relationships with manufacturers of bisphosphonates.

The task force report is available at www.jbmr.org/details/journalArticle/843323/Atypical_subtrochanteric_and_diaphyseal_femoral_fractures_Report_of_a_task_force.htmlwww.fda.gov/medwatch

This anterior-posterior radiograph of the left femur demonstrates a substantially transverse femoral fracture and associated diffuse periosteal new bone formation (black arrow) and focal cortical thickening (white arrow), consistent with atypical femoral shaft fracture.

Source Courtesy American Society for Bone and Mineral Research

Long-term treatment with bisphosphonates may be related to an increased risk of atypical femur fractures in patients, who may experience weeks or even months of pain before fracture diagnosis, according to the final report issued by a task force convened by the American Society of Bone and Mineral Research.

The society created the international, multidisciplinary task force to address reports of “atypical fractures of the subtrochanteric region of the hip and the femoral shaft” in patients on long-term bisphosphonate therapy. A statement issued by the society announcing the release of the report referred to it as “the most comprehensive scientific report to date” on this issue. The task force based its report on findings from a review of published and unpublished data, interviews with scientists at companies that manufacture these drugs, and Food and Drug Administration data.

The review included an analysis of 310 published case reports of patients (aged 36-92 years) with atypical subtrochanteric and femoral shaft fractures. Of these patients, 291 (94%) had been treated with bisphosphonates, mostly for osteoporosis. The median duration of treatment was 7 years, and most were treated for more than 5 years, according to the report, which points out that these fractures are rare, accounting for less than 1% of the overall rate of hip and femur fractures (J. Bone Miner. Res. 2010 Sept. 14 [doi:10.1002/jbmr.253]).

More than half of the patients with such femur fractures had experienced a prodrome of pain in the groin or thigh for weeks or months, and fractures were bilateral in more than 25% of the patients.

“We are concerned that there may be a relationship between these fractures and long-term bisphosphonate use and, although the risk is low, we want to make sure that people know about the warning signs,” the task force cochair and lead author of the report, Dr. Elizabeth Shane, said in the ASBMR statement. “Health professionals should know the warning signs of atypical femur fractures, and regularly ask patients on these drugs about groin or thigh pain,” added Dr. Shane, professor of medicine at Columbia University in New York.

She also recommended that every year, clinicians evaluate whether bisphosphonate therapy is appropriate for patients on these drugs, and that the drugs “be reserved” for patients with Paget's disease, patients with osteoporosis who are at high risk of fractures, and patients with certain cancers, she added.

In the statement, Dr. Shane said that for the “vast majority of patients with osteoporosis, these drugs are an important weapon against fractures and their benefits far outweigh the risks.”

The ASBMR task force recommendations include establishing an international registry of patients with these fractures, increasing research to determine whether bisphosphonates are the cause, and improving the labeling of these products so that health care professionals and patients are more aware of the potential for these fractures and the associated symptoms.

A statement issued by the FDA said the agency “recommends that health care professionals be aware of the possible risk of unusual femur fractures in patients taking bisphosphonates. Patients should talk to their health care professional if they develop new thigh or groin pain so that they may be evaluated to rule out a femur fracture.”

Dr. Shane and other members of the task force disclosed relationships with manufacturers of bisphosphonates.

The task force report is available at www.jbmr.org/details/journalArticle/843323/Atypical_subtrochanteric_and_diaphyseal_femoral_fractures_Report_of_a_task_force.htmlwww.fda.gov/medwatch

This anterior-posterior radiograph of the left femur demonstrates a substantially transverse femoral fracture and associated diffuse periosteal new bone formation (black arrow) and focal cortical thickening (white arrow), consistent with atypical femoral shaft fracture.

Source Courtesy American Society for Bone and Mineral Research

The Food and Drug Administration is encouraging health care professionals to report any adverse events associated with over-the-counter products marketed to patients as chelation treatments for various diseases. These products have not been approved by the FDA for any indication and are potentially dangerous.

During an Oct. 14 briefing, FDA officials said that warning letters had been sent to eight manufacturers of these products, saying that they are considered unapproved drugs and devices and that making unproven claims about the products violates federal law. If the companies don’t comply, they may be subjected to further legal action, including seizure of the products.

The FDA has not received any formal reports of severe adverse events associated with these products. Dr. Charles Lee, a medical officer in the division of new drugs and labeling compliance in the FDA’s Center for Drug Evaluation and Research, said that the risks of these products include dehydration, kidney failure, and death.

The companies have made claims that their products treat a variety of diseases by removing toxic chemicals and heavy metals from the body. Some of the companies also make tests that they claim can detect the presence of heavy metals to determine if chelation therapy is needed, the agency said.

Despite these claims, “the effectiveness in treating any of the diseases listed is unsubstantiated,” the statement said. The products— which are widely available on the Internet and come in transmucosal sprays, suppositories, capsules, liquid drops, clay baths, and other formulations— are marketed to treat the following conditions, including: cardiovascular diseases, Parkinson’s disease, Alzheimer’s disease, macular degeneration, and autism spectrum disorder.

FDA-approved chelation therapies are approved only as prescription products; screening tests are considered devices and also require FDA approval.

The products covered in the warning letter include “Advanced Formula EDTA Oral Chelation,” which the manufacturer claims can unclog arteries, dissolve plaque, lower cholesterol, and prevent heart attacks. Another company promoted patient claims that its Kelatox suppository had almost completely eliminated peripheral neuropathy symptoms. One company’s clay baths are touted for their ability to remove chemical toxins that include food additives, cigarette toxins, and pesticides, and for producing “dramatic” improvements in children with autism.

Adverse events associated with these products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration is encouraging health care professionals to report any adverse events associated with over-the-counter products marketed to patients as chelation treatments for various diseases. These products have not been approved by the FDA for any indication and are potentially dangerous.

During an Oct. 14 briefing, FDA officials said that warning letters had been sent to eight manufacturers of these products, saying that they are considered unapproved drugs and devices and that making unproven claims about the products violates federal law. If the companies don’t comply, they may be subjected to further legal action, including seizure of the products.

The FDA has not received any formal reports of severe adverse events associated with these products. Dr. Charles Lee, a medical officer in the division of new drugs and labeling compliance in the FDA’s Center for Drug Evaluation and Research, said that the risks of these products include dehydration, kidney failure, and death.

The companies have made claims that their products treat a variety of diseases by removing toxic chemicals and heavy metals from the body. Some of the companies also make tests that they claim can detect the presence of heavy metals to determine if chelation therapy is needed, the agency said.

Despite these claims, “the effectiveness in treating any of the diseases listed is unsubstantiated,” the statement said. The products— which are widely available on the Internet and come in transmucosal sprays, suppositories, capsules, liquid drops, clay baths, and other formulations— are marketed to treat the following conditions, including: cardiovascular diseases, Parkinson’s disease, Alzheimer’s disease, macular degeneration, and autism spectrum disorder.

FDA-approved chelation therapies are approved only as prescription products; screening tests are considered devices and also require FDA approval.

The products covered in the warning letter include “Advanced Formula EDTA Oral Chelation,” which the manufacturer claims can unclog arteries, dissolve plaque, lower cholesterol, and prevent heart attacks. Another company promoted patient claims that its Kelatox suppository had almost completely eliminated peripheral neuropathy symptoms. One company’s clay baths are touted for their ability to remove chemical toxins that include food additives, cigarette toxins, and pesticides, and for producing “dramatic” improvements in children with autism.

Adverse events associated with these products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration is encouraging health care professionals to report any adverse events associated with over-the-counter products marketed to patients as chelation treatments for various diseases. These products have not been approved by the FDA for any indication and are potentially dangerous.

During an Oct. 14 briefing, FDA officials said that warning letters had been sent to eight manufacturers of these products, saying that they are considered unapproved drugs and devices and that making unproven claims about the products violates federal law. If the companies don’t comply, they may be subjected to further legal action, including seizure of the products.

The FDA has not received any formal reports of severe adverse events associated with these products. Dr. Charles Lee, a medical officer in the division of new drugs and labeling compliance in the FDA’s Center for Drug Evaluation and Research, said that the risks of these products include dehydration, kidney failure, and death.

The companies have made claims that their products treat a variety of diseases by removing toxic chemicals and heavy metals from the body. Some of the companies also make tests that they claim can detect the presence of heavy metals to determine if chelation therapy is needed, the agency said.

Despite these claims, “the effectiveness in treating any of the diseases listed is unsubstantiated,” the statement said. The products— which are widely available on the Internet and come in transmucosal sprays, suppositories, capsules, liquid drops, clay baths, and other formulations— are marketed to treat the following conditions, including: cardiovascular diseases, Parkinson’s disease, Alzheimer’s disease, macular degeneration, and autism spectrum disorder.

FDA-approved chelation therapies are approved only as prescription products; screening tests are considered devices and also require FDA approval.

The products covered in the warning letter include “Advanced Formula EDTA Oral Chelation,” which the manufacturer claims can unclog arteries, dissolve plaque, lower cholesterol, and prevent heart attacks. Another company promoted patient claims that its Kelatox suppository had almost completely eliminated peripheral neuropathy symptoms. One company’s clay baths are touted for their ability to remove chemical toxins that include food additives, cigarette toxins, and pesticides, and for producing “dramatic” improvements in children with autism.

Adverse events associated with these products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration on Oct. 13 issued a warning about the “possible” risk of the rare atypical femur fractures associated with bisphosphonate treatment in osteoporosis patients, after reviewing the final report on this association released last month by the American Society for Bone and Mineral Research.

The FDA has requested that a warning about the association be added to the labels of all bisphosphonates approved for osteoporosis prevention and treatment, and that a medication guide explaining the risk and the symptoms of these fractures be provided to patients with each bisphosphonate prescription, said Dr. Sandra Kweder during an Oct. 13 briefing.

The agency is also requiring a change to the “indications and usage” section of the bisphosphonate labels, which will highlight that the optimal duration of treatment with bisphosphonates is not clear when they are used to treat and/or prevent osteoporosis.

In March 2010, the FDA announced that the agency was reviewing reports of femur fractures associated with bisphosphonate use, and in September, a report issued by an American Society for Bone and Mineral Research (ASBMR) task force concluded that long-term bisphosphonate treatment may be related to an increased risk of these fractures, described as atypical fractures of the subtrochanteric region of the hip and femoral shaft.

The ASBMR report “helped us understand these fractures a little bit better and makes us confident that this is something that is potentially more closely related to these drugs, particularly [during] long-term use, than we previously had evidence for,” said Dr. Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

These fractures affect the femoral shaft, are less likely to be associated with trauma than are typical osteoporotic fractures, are sometimes bilateral, and generally affect younger patients, she said. Affected patients have described dull aching thigh or groin pain weeks to months before complete fracture is identified, she noted. The data indicate that they are more common in patients who have been on treatment for more than 5 years.

Similar to the recommendations made in the ASBMR report, the FDA’s recommendations to health care professionals include evaluating any patient who presents with new thigh or groin pain for a femur fracture, stopping treatment in patients with evidence of a femoral shaft fracture, and periodically re-evaluating the need for continued treatment, particularly in patients treated for more than 5 years.

The products affected are those approved for osteoporosis indications, such as alendronate (Fosamax), alendronate and cholecalciferol (Fosamax Plus D), risedronate sodium (Actonel), risedronate sodium with calcium carbonate (Actonel with Calcium), ibandronate sodium (Boniva), risedronate sodium (Atelvia), pamidronate injection (Aredia), and zoledronic acid injection (Reclast), as well as generic formulations of those drugs.

The ASBMR report was released on Sept. 14.

The FDA advisory is available at www.fda.gov/Drugs/DrugSafety/ucm229009.htm. Serious adverse events associated with bisphosphonates should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration on Oct. 13 issued a warning about the “possible” risk of the rare atypical femur fractures associated with bisphosphonate treatment in osteoporosis patients, after reviewing the final report on this association released last month by the American Society for Bone and Mineral Research.

The FDA has requested that a warning about the association be added to the labels of all bisphosphonates approved for osteoporosis prevention and treatment, and that a medication guide explaining the risk and the symptoms of these fractures be provided to patients with each bisphosphonate prescription, said Dr. Sandra Kweder during an Oct. 13 briefing.

The agency is also requiring a change to the “indications and usage” section of the bisphosphonate labels, which will highlight that the optimal duration of treatment with bisphosphonates is not clear when they are used to treat and/or prevent osteoporosis.

In March 2010, the FDA announced that the agency was reviewing reports of femur fractures associated with bisphosphonate use, and in September, a report issued by an American Society for Bone and Mineral Research (ASBMR) task force concluded that long-term bisphosphonate treatment may be related to an increased risk of these fractures, described as atypical fractures of the subtrochanteric region of the hip and femoral shaft.

The ASBMR report “helped us understand these fractures a little bit better and makes us confident that this is something that is potentially more closely related to these drugs, particularly [during] long-term use, than we previously had evidence for,” said Dr. Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

These fractures affect the femoral shaft, are less likely to be associated with trauma than are typical osteoporotic fractures, are sometimes bilateral, and generally affect younger patients, she said. Affected patients have described dull aching thigh or groin pain weeks to months before complete fracture is identified, she noted. The data indicate that they are more common in patients who have been on treatment for more than 5 years.

Similar to the recommendations made in the ASBMR report, the FDA’s recommendations to health care professionals include evaluating any patient who presents with new thigh or groin pain for a femur fracture, stopping treatment in patients with evidence of a femoral shaft fracture, and periodically re-evaluating the need for continued treatment, particularly in patients treated for more than 5 years.

The products affected are those approved for osteoporosis indications, such as alendronate (Fosamax), alendronate and cholecalciferol (Fosamax Plus D), risedronate sodium (Actonel), risedronate sodium with calcium carbonate (Actonel with Calcium), ibandronate sodium (Boniva), risedronate sodium (Atelvia), pamidronate injection (Aredia), and zoledronic acid injection (Reclast), as well as generic formulations of those drugs.

The ASBMR report was released on Sept. 14.

The FDA advisory is available at www.fda.gov/Drugs/DrugSafety/ucm229009.htm. Serious adverse events associated with bisphosphonates should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration on Oct. 13 issued a warning about the “possible” risk of the rare atypical femur fractures associated with bisphosphonate treatment in osteoporosis patients, after reviewing the final report on this association released last month by the American Society for Bone and Mineral Research.

The FDA has requested that a warning about the association be added to the labels of all bisphosphonates approved for osteoporosis prevention and treatment, and that a medication guide explaining the risk and the symptoms of these fractures be provided to patients with each bisphosphonate prescription, said Dr. Sandra Kweder during an Oct. 13 briefing.

The agency is also requiring a change to the “indications and usage” section of the bisphosphonate labels, which will highlight that the optimal duration of treatment with bisphosphonates is not clear when they are used to treat and/or prevent osteoporosis.

In March 2010, the FDA announced that the agency was reviewing reports of femur fractures associated with bisphosphonate use, and in September, a report issued by an American Society for Bone and Mineral Research (ASBMR) task force concluded that long-term bisphosphonate treatment may be related to an increased risk of these fractures, described as atypical fractures of the subtrochanteric region of the hip and femoral shaft.

The ASBMR report “helped us understand these fractures a little bit better and makes us confident that this is something that is potentially more closely related to these drugs, particularly [during] long-term use, than we previously had evidence for,” said Dr. Kweder, deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research.

These fractures affect the femoral shaft, are less likely to be associated with trauma than are typical osteoporotic fractures, are sometimes bilateral, and generally affect younger patients, she said. Affected patients have described dull aching thigh or groin pain weeks to months before complete fracture is identified, she noted. The data indicate that they are more common in patients who have been on treatment for more than 5 years.

Similar to the recommendations made in the ASBMR report, the FDA’s recommendations to health care professionals include evaluating any patient who presents with new thigh or groin pain for a femur fracture, stopping treatment in patients with evidence of a femoral shaft fracture, and periodically re-evaluating the need for continued treatment, particularly in patients treated for more than 5 years.

The products affected are those approved for osteoporosis indications, such as alendronate (Fosamax), alendronate and cholecalciferol (Fosamax Plus D), risedronate sodium (Actonel), risedronate sodium with calcium carbonate (Actonel with Calcium), ibandronate sodium (Boniva), risedronate sodium (Atelvia), pamidronate injection (Aredia), and zoledronic acid injection (Reclast), as well as generic formulations of those drugs.

The ASBMR report was released on Sept. 14.

The FDA advisory is available at www.fda.gov/Drugs/DrugSafety/ucm229009.htm. Serious adverse events associated with bisphosphonates should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The injectable extended-release formulation of naltrexone, marketed as Vivitrol, has been approved as a treatment for preventing relapses in people who have undergone opioid detoxification, the Food and Drug Administration announced Oct. 13.

Vivitrol, approved in 2006 for the treatment of alcohol dependence, is administered in an intramuscular injection once a month, in patients who have no opioids remaining in their system. If opioids are present, patients may experience withdrawal symptoms, according to the FDA statement. Naltrexone is an opioid antagonist.

Approval was based on the results of a 6-month study of 250 patients who were completing or had recently completed detoxification and were no longer physically dependent on opioids. Between the 5th week and the end of the study, 36% of those treated with Vivitrol (one 380-mg injection once a month) had not used opioids at all, compared with 23% of those on placebo, a significant difference. All patients received psychosocial support during the study.

Side effects associated with Vivitrol treatment include nausea, fatigue, headache, dizziness, vomiting, reduced appetite, painful joints, and muscle cramps, the FDA statement said. Serious side effects include injection site reactions, allergic reactions, hepatotoxicity, and depression, as well as suicide and suicidal thoughts and behavior.

Customized needles provided in the Vivitrol package must be used to inject the medication as an intramuscular gluteal injection, according to the FDA and Alkermes Inc., the manufacturer of Vivitrol.

In the FDA statement, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, described the approval as “a significant advancement in addiction treatment.”

The FDA has asked the company to conduct postmarketing pharmacokinetic and efficacy studies of Vivitrol in patients aged 12-16 years.

Serious adverse reactions associated with Vivitrol should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The injectable extended-release formulation of naltrexone, marketed as Vivitrol, has been approved as a treatment for preventing relapses in people who have undergone opioid detoxification, the Food and Drug Administration announced Oct. 13.

Vivitrol, approved in 2006 for the treatment of alcohol dependence, is administered in an intramuscular injection once a month, in patients who have no opioids remaining in their system. If opioids are present, patients may experience withdrawal symptoms, according to the FDA statement. Naltrexone is an opioid antagonist.

Approval was based on the results of a 6-month study of 250 patients who were completing or had recently completed detoxification and were no longer physically dependent on opioids. Between the 5th week and the end of the study, 36% of those treated with Vivitrol (one 380-mg injection once a month) had not used opioids at all, compared with 23% of those on placebo, a significant difference. All patients received psychosocial support during the study.

Side effects associated with Vivitrol treatment include nausea, fatigue, headache, dizziness, vomiting, reduced appetite, painful joints, and muscle cramps, the FDA statement said. Serious side effects include injection site reactions, allergic reactions, hepatotoxicity, and depression, as well as suicide and suicidal thoughts and behavior.

Customized needles provided in the Vivitrol package must be used to inject the medication as an intramuscular gluteal injection, according to the FDA and Alkermes Inc., the manufacturer of Vivitrol.

In the FDA statement, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, described the approval as “a significant advancement in addiction treatment.”

The FDA has asked the company to conduct postmarketing pharmacokinetic and efficacy studies of Vivitrol in patients aged 12-16 years.

Serious adverse reactions associated with Vivitrol should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The injectable extended-release formulation of naltrexone, marketed as Vivitrol, has been approved as a treatment for preventing relapses in people who have undergone opioid detoxification, the Food and Drug Administration announced Oct. 13.

Vivitrol, approved in 2006 for the treatment of alcohol dependence, is administered in an intramuscular injection once a month, in patients who have no opioids remaining in their system. If opioids are present, patients may experience withdrawal symptoms, according to the FDA statement. Naltrexone is an opioid antagonist.

Approval was based on the results of a 6-month study of 250 patients who were completing or had recently completed detoxification and were no longer physically dependent on opioids. Between the 5th week and the end of the study, 36% of those treated with Vivitrol (one 380-mg injection once a month) had not used opioids at all, compared with 23% of those on placebo, a significant difference. All patients received psychosocial support during the study.

Side effects associated with Vivitrol treatment include nausea, fatigue, headache, dizziness, vomiting, reduced appetite, painful joints, and muscle cramps, the FDA statement said. Serious side effects include injection site reactions, allergic reactions, hepatotoxicity, and depression, as well as suicide and suicidal thoughts and behavior.

Customized needles provided in the Vivitrol package must be used to inject the medication as an intramuscular gluteal injection, according to the FDA and Alkermes Inc., the manufacturer of Vivitrol.

In the FDA statement, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, described the approval as “a significant advancement in addiction treatment.”

The FDA has asked the company to conduct postmarketing pharmacokinetic and efficacy studies of Vivitrol in patients aged 12-16 years.

Serious adverse reactions associated with Vivitrol should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

The Food and Drug Administration has decided that the sedative-hypnotic drug sodium oxybate cannot be approved for treatment of fibromyalgia, based on the information currently included in the approval application, the manufacturer announced on Oct. 11.

The statement issued by Jazz Pharmaceuticals noted that the FDA’s “complete response letter” said that the new drug application for sodium oxybate cannot be approved “in its present form” and cited the need for more clinical studies. The FDA’s letter also discusses the proposed Risk Evaluation and Mitigation Strategy (REMS), as well as the concentration and trade name for sodium oxybate, according to Jazz.

Other topics discussed in the letter include the need for methods to ensure safe use of the drug, the sodium salt of gamma hydroxybutyrate, an endogenous neurotransmitter synthesized from gamma aminobutyric acid, which is also known as the “date rape” drug for its potent sedative effects.

It is the FDA’s practice to send complete response letters to sponsors of new drug applications when there are concerns about whether the drug should be approved and to outline information needed to complete the approval process. The agency does not comment on products under review, and therefore does not release information on these letters; it is up to the companies to release this information.

The concerns that the Jazz statement said were outlined in the letter reflect those expressed by members of two FDA advisory panels at an August meeting held to review the data on sodium oxybate for the fibromyalgia indication. At the meeting, the majority of the panelists voted against recommending approval, citing the lack of long-term data and other concerns regarding the drug – including its potential for illicit use. The drug’s only approved indication is for the treatment of narcolepsy, a fairly uncommon condition. Were sodium oxybate to be approved for fibromyalgia, which is more common, it is possible that the drug would be more likely to be misused because it would be present in more family medicine cabinets.

Sodium oxybate is also the active ingredient in Xyrem, which is approved for treating excessive daytime sleepiness and cataplexy in adults with narcolepsy. The availability of Xyrem is tightly controlled through a REMS, which includes restricted distribution through one centralized pharmacy. The company had proposed that the drug be marketed under a different trade name for fibromyalgia, with a different REMS, which panelists said could be confusing and could increase medical errors.

The company proposed that patients would take two doses, one before going to sleep and the second in the middle of the night, which was also cited as a disadvantage for patients. Panelists were also concerned that leaving the second dose by the bedside table could increase the chance it would be used illicitly or ingested accidentally by children.

In two phase III, randomized, double-blind, controlled 14-week studies, two different doses of sodium oxybate were compared to placebo in about 1,000 fibromyalgia patients aged 18 years and older. All the patients discontinued opiates, benzodiazepines, muscle relaxants, and other medications or devices before enrollment. A significantly greater proportion of those treated with sodium oxybate (36%-46%) met the primary end point, at least a 30% reduction in pain from baseline to the end of treatment, compared with those on placebo (20%-27%). Adverse events were similar to those observed in Xyrem trials.

The Jazz statement says that the company has requested a meeting with the FDA to discuss the complete response letter, and will then evaluate the next steps for the drug, which the company believes could meet a “significant unmet medical need among fibromyalgia patients,” if approved, Bruce Cozadd, chairman and chief executive officer at Jazz said in the statement.

Xyrem is also approved in the European Union and Canada for treating symptoms associated with narcolepsy. The drugs currently approved for treating fibromyalgia in the United States are milnacipran (Savella), pregabalin (Lyrica), and duloxetine (Cymbalta).

Abbott Laboratories is voluntarily withdrawing sibutramine from the market based on an increased risk of myocardial infarction and stroke in those taking the drug, a risk that outweighs “any benefit from the modest weight loss observed with the drug,” the Food and Drug Administration announced Oct. 8.

“Physicians are advised to stop prescribing Meridia to their patients,” Dr. John Jenkins, director of the office of new drugs at FDA’s Center for Drug Evaluation and Research (CDER), said during a press briefing.

The decision was based on results from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, a postmarketing study conducted at the request of European health authorities, which found that the risk of major adverse cardiovascular events (a composite of nonfatal heart attack, nonfatal stroke, resuscitation after cardiac arrest, and cardiovascular death) was 16% higher among sibutramine-treated patients compared with those on placebo. After 60 months, those on sibutramine had lost a small amount of weight on average compared with those on placebo.

Sibutramine was withdrawn from the European market in January, based on the SCOUT results.

Most of the patients in SCOUT – who had pre-existing cardiovascular disease, type 2 diabetes, or both – would not be considered candidates for treatment, based on the labeling in the United States. But during the briefing, Dr. Gerald Dal Pan, director of CDER’s Office of Surveillance and Epidemiology, said that “these results, combined with other available safety data raised serious questions about Meridia’s safety for all patient groups.”

The FDA recommends that clinicians contact patients taking sibutramine and advise them to stop. Clinicians also are advised to evaluate these patients for cardiovascular events if they present with any signs or symptoms of cardiovascular disease, according to the agency.

The announcement was made almost 13 years after sibutramine was approved by the FDA – and less than a month after half of the members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee panel recommended that it be taken off the market.

Small average increases in heart rate and blood pressure associated with treatment were a concern when sibutramine was approved; however, the drug was approved because of the cardiovascular and other health benefits expected with weight loss, and because heart rate and blood pressure can be easily monitored, Dr. Jenkins explained.

About 100,000 people in the United States currently take sibutramine, Dr. Dal Pan said. At the advisory panel meeting in September, the FDA presented outpatient prescription data, showing an almost 81% drop in sibutramine prescriptions in the United States between 1998 and 2009.

Also on Oct. 8, the FDA advised individuals not to take “Slimming Beauty Bitter Orange Slimming Capsules,” a product sold over the Internet. The product contains “excessive amounts of sibutramine that may be dangerous to people who have a history of cardiovascular disease,” according to FDA, which noted there have been reports of serious side effects associated with the product, including elevated blood pressure, headaches, vomiting, and insomnia.

The FDA is encouraging clinicians to report adverse events associated with sibutramine to the MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

Abbott Laboratories is voluntarily withdrawing sibutramine from the market based on an increased risk of myocardial infarction and stroke in those taking the drug, a risk that outweighs “any benefit from the modest weight loss observed with the drug,” the Food and Drug Administration announced Oct. 8.

“Physicians are advised to stop prescribing Meridia to their patients,” Dr. John Jenkins, director of the office of new drugs at FDA’s Center for Drug Evaluation and Research (CDER), said during a press briefing.

The decision was based on results from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, a postmarketing study conducted at the request of European health authorities, which found that the risk of major adverse cardiovascular events (a composite of nonfatal heart attack, nonfatal stroke, resuscitation after cardiac arrest, and cardiovascular death) was 16% higher among sibutramine-treated patients compared with those on placebo. After 60 months, those on sibutramine had lost a small amount of weight on average compared with those on placebo.

Sibutramine was withdrawn from the European market in January, based on the SCOUT results.

Most of the patients in SCOUT – who had pre-existing cardiovascular disease, type 2 diabetes, or both – would not be considered candidates for treatment, based on the labeling in the United States. But during the briefing, Dr. Gerald Dal Pan, director of CDER’s Office of Surveillance and Epidemiology, said that “these results, combined with other available safety data raised serious questions about Meridia’s safety for all patient groups.”

The FDA recommends that clinicians contact patients taking sibutramine and advise them to stop. Clinicians also are advised to evaluate these patients for cardiovascular events if they present with any signs or symptoms of cardiovascular disease, according to the agency.

The announcement was made almost 13 years after sibutramine was approved by the FDA – and less than a month after half of the members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee panel recommended that it be taken off the market.

Small average increases in heart rate and blood pressure associated with treatment were a concern when sibutramine was approved; however, the drug was approved because of the cardiovascular and other health benefits expected with weight loss, and because heart rate and blood pressure can be easily monitored, Dr. Jenkins explained.

About 100,000 people in the United States currently take sibutramine, Dr. Dal Pan said. At the advisory panel meeting in September, the FDA presented outpatient prescription data, showing an almost 81% drop in sibutramine prescriptions in the United States between 1998 and 2009.

Also on Oct. 8, the FDA advised individuals not to take “Slimming Beauty Bitter Orange Slimming Capsules,” a product sold over the Internet. The product contains “excessive amounts of sibutramine that may be dangerous to people who have a history of cardiovascular disease,” according to FDA, which noted there have been reports of serious side effects associated with the product, including elevated blood pressure, headaches, vomiting, and insomnia.

The FDA is encouraging clinicians to report adverse events associated with sibutramine to the MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

Abbott Laboratories is voluntarily withdrawing sibutramine from the market based on an increased risk of myocardial infarction and stroke in those taking the drug, a risk that outweighs “any benefit from the modest weight loss observed with the drug,” the Food and Drug Administration announced Oct. 8.

“Physicians are advised to stop prescribing Meridia to their patients,” Dr. John Jenkins, director of the office of new drugs at FDA’s Center for Drug Evaluation and Research (CDER), said during a press briefing.

The decision was based on results from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, a postmarketing study conducted at the request of European health authorities, which found that the risk of major adverse cardiovascular events (a composite of nonfatal heart attack, nonfatal stroke, resuscitation after cardiac arrest, and cardiovascular death) was 16% higher among sibutramine-treated patients compared with those on placebo. After 60 months, those on sibutramine had lost a small amount of weight on average compared with those on placebo.

Sibutramine was withdrawn from the European market in January, based on the SCOUT results.

Most of the patients in SCOUT – who had pre-existing cardiovascular disease, type 2 diabetes, or both – would not be considered candidates for treatment, based on the labeling in the United States. But during the briefing, Dr. Gerald Dal Pan, director of CDER’s Office of Surveillance and Epidemiology, said that “these results, combined with other available safety data raised serious questions about Meridia’s safety for all patient groups.”

The FDA recommends that clinicians contact patients taking sibutramine and advise them to stop. Clinicians also are advised to evaluate these patients for cardiovascular events if they present with any signs or symptoms of cardiovascular disease, according to the agency.

The announcement was made almost 13 years after sibutramine was approved by the FDA – and less than a month after half of the members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee panel recommended that it be taken off the market.

Small average increases in heart rate and blood pressure associated with treatment were a concern when sibutramine was approved; however, the drug was approved because of the cardiovascular and other health benefits expected with weight loss, and because heart rate and blood pressure can be easily monitored, Dr. Jenkins explained.

About 100,000 people in the United States currently take sibutramine, Dr. Dal Pan said. At the advisory panel meeting in September, the FDA presented outpatient prescription data, showing an almost 81% drop in sibutramine prescriptions in the United States between 1998 and 2009.

Also on Oct. 8, the FDA advised individuals not to take “Slimming Beauty Bitter Orange Slimming Capsules,” a product sold over the Internet. The product contains “excessive amounts of sibutramine that may be dangerous to people who have a history of cardiovascular disease,” according to FDA, which noted there have been reports of serious side effects associated with the product, including elevated blood pressure, headaches, vomiting, and insomnia.

The FDA is encouraging clinicians to report adverse events associated with sibutramine to the MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.