Elizabeth Mechcatie

ROCKVILLE, MD. — More than 11,000 perioperative medication errors were reported to a national database between 1998 and 2005. Of these, 5% resulted in harm, according to a report issued by the United States Pharmacopeia.

The database, known as MEDMARX, is operated by the USP and is the largest national database of hospital medication errors in the United States, receiving about 15,000 new reports every month.

The 11,239 perioperative medication errors reported by more than 500 hospitals in 7 years were divided into four settings: outpatient surgery (30% of the total reports), the preoperative holding area (7%), the operating room (34%), and the postanesthesia care unit (29%). The proportion reported in the preoperative holding area was lower because this category was added to the database in 2003.

The 5% rate of harmful errors is about threefold higher than the proportion of medication errors resulting in harm in all other areas of the hospital combined. Harmful errors occurred in all four perioperative areas but were most common in the operating room. The proportion of perioperative medication errors that resulted in harm was higher among patients under age 17 than it was among older patients.

Among the medication errors that resulted in harm, there were four deaths, including one pediatric patient, according to Diane D. Cousins, a registered pharmacist and vice president of the Center for the Advancement of Patient Safety at the USP.

A total of 739 drug products were involved in errors, the most common of which were the antibiotics cefazolin and vancomycin; the analgesics morphine, fentanyl, and meperidine; the sedative midazolam; and heparin, Ms. Cousins said. There were 165 drugs (22%) involved in harmful errors; most common among them were morphine, fentanyl, and cefazolin. Errors included administering the wrong medication or the wrong amount of medication, administering medication at the wrong time, omitting a medication or a dose, or administering medication incorrectly.

In the operating room, omission and wrong drug administration were the most common mistakes, she said. For example, a surgeon called in an order for a dose of ampicillin to be given during surgery that was scheduled a week later, but the order was never recorded. As a result, the patient (a child) never received the drug.

In the postanesthesia care unit setting, the most typical errors involved prescribing and administering incorrect amounts of drugs, she said. After an elderly patient was discharged from the postanesthesia care unit to an inpatient unit, it was discovered that the patient was receiving an excessive amount of heparin because of a programming error made in the postanesthesia care unit.

The results were announced at a press briefing sponsored by the USP, which released the report in partnership with the Uniformed Services University of the Health Sciences (USUHS), the Association of PeriOperative Registered Nurses (AORN), and the American Society of PeriAnesthesia Nurses (ASPAN).

Published by the USP Center for the Advancement of Patient Safety, the report is the largest known national analysis of medication errors related to surgery, Ms. Cousins said at the briefing.

The findings were also provided in a briefing to 11 national organizations and agencies, with the intention of calling them to action and to “mobilize not only the organizations but their membership to develop risk-prevention strategies that will make their patient care safer,” Ms. Cousins said.

The 47 recommendations issued in the report include implementing strategies that improve communication among all perioperative team members, designating a pharmacist to coordinate medication safety, and working to ensure that medications are administered on time.

The report is available (for purchase) at www.usp.org/products/medMarx

ROCKVILLE, MD. — More than 11,000 perioperative medication errors were reported to a national database between 1998 and 2005. Of these, 5% resulted in harm, according to a report issued by the United States Pharmacopeia.

The database, known as MEDMARX, is operated by the USP and is the largest national database of hospital medication errors in the United States, receiving about 15,000 new reports every month.

The 11,239 perioperative medication errors reported by more than 500 hospitals in 7 years were divided into four settings: outpatient surgery (30% of the total reports), the preoperative holding area (7%), the operating room (34%), and the postanesthesia care unit (29%). The proportion reported in the preoperative holding area was lower because this category was added to the database in 2003.

The 5% rate of harmful errors is about threefold higher than the proportion of medication errors resulting in harm in all other areas of the hospital combined. Harmful errors occurred in all four perioperative areas but were most common in the operating room. The proportion of perioperative medication errors that resulted in harm was higher among patients under age 17 than it was among older patients.

Among the medication errors that resulted in harm, there were four deaths, including one pediatric patient, according to Diane D. Cousins, a registered pharmacist and vice president of the Center for the Advancement of Patient Safety at the USP.

A total of 739 drug products were involved in errors, the most common of which were the antibiotics cefazolin and vancomycin; the analgesics morphine, fentanyl, and meperidine; the sedative midazolam; and heparin, Ms. Cousins said. There were 165 drugs (22%) involved in harmful errors; most common among them were morphine, fentanyl, and cefazolin. Errors included administering the wrong medication or the wrong amount of medication, administering medication at the wrong time, omitting a medication or a dose, or administering medication incorrectly.

In the operating room, omission and wrong drug administration were the most common mistakes, she said. For example, a surgeon called in an order for a dose of ampicillin to be given during surgery that was scheduled a week later, but the order was never recorded. As a result, the patient (a child) never received the drug.

In the postanesthesia care unit setting, the most typical errors involved prescribing and administering incorrect amounts of drugs, she said. After an elderly patient was discharged from the postanesthesia care unit to an inpatient unit, it was discovered that the patient was receiving an excessive amount of heparin because of a programming error made in the postanesthesia care unit.

The results were announced at a press briefing sponsored by the USP, which released the report in partnership with the Uniformed Services University of the Health Sciences (USUHS), the Association of PeriOperative Registered Nurses (AORN), and the American Society of PeriAnesthesia Nurses (ASPAN).

Published by the USP Center for the Advancement of Patient Safety, the report is the largest known national analysis of medication errors related to surgery, Ms. Cousins said at the briefing.

The findings were also provided in a briefing to 11 national organizations and agencies, with the intention of calling them to action and to “mobilize not only the organizations but their membership to develop risk-prevention strategies that will make their patient care safer,” Ms. Cousins said.

The 47 recommendations issued in the report include implementing strategies that improve communication among all perioperative team members, designating a pharmacist to coordinate medication safety, and working to ensure that medications are administered on time.

The report is available (for purchase) at www.usp.org/products/medMarx

ROCKVILLE, MD. — More than 11,000 perioperative medication errors were reported to a national database between 1998 and 2005. Of these, 5% resulted in harm, according to a report issued by the United States Pharmacopeia.

The database, known as MEDMARX, is operated by the USP and is the largest national database of hospital medication errors in the United States, receiving about 15,000 new reports every month.

The 11,239 perioperative medication errors reported by more than 500 hospitals in 7 years were divided into four settings: outpatient surgery (30% of the total reports), the preoperative holding area (7%), the operating room (34%), and the postanesthesia care unit (29%). The proportion reported in the preoperative holding area was lower because this category was added to the database in 2003.

The 5% rate of harmful errors is about threefold higher than the proportion of medication errors resulting in harm in all other areas of the hospital combined. Harmful errors occurred in all four perioperative areas but were most common in the operating room. The proportion of perioperative medication errors that resulted in harm was higher among patients under age 17 than it was among older patients.

Among the medication errors that resulted in harm, there were four deaths, including one pediatric patient, according to Diane D. Cousins, a registered pharmacist and vice president of the Center for the Advancement of Patient Safety at the USP.

A total of 739 drug products were involved in errors, the most common of which were the antibiotics cefazolin and vancomycin; the analgesics morphine, fentanyl, and meperidine; the sedative midazolam; and heparin, Ms. Cousins said. There were 165 drugs (22%) involved in harmful errors; most common among them were morphine, fentanyl, and cefazolin. Errors included administering the wrong medication or the wrong amount of medication, administering medication at the wrong time, omitting a medication or a dose, or administering medication incorrectly.

In the operating room, omission and wrong drug administration were the most common mistakes, she said. For example, a surgeon called in an order for a dose of ampicillin to be given during surgery that was scheduled a week later, but the order was never recorded. As a result, the patient (a child) never received the drug.

In the postanesthesia care unit setting, the most typical errors involved prescribing and administering incorrect amounts of drugs, she said. After an elderly patient was discharged from the postanesthesia care unit to an inpatient unit, it was discovered that the patient was receiving an excessive amount of heparin because of a programming error made in the postanesthesia care unit.

The results were announced at a press briefing sponsored by the USP, which released the report in partnership with the Uniformed Services University of the Health Sciences (USUHS), the Association of PeriOperative Registered Nurses (AORN), and the American Society of PeriAnesthesia Nurses (ASPAN).

Published by the USP Center for the Advancement of Patient Safety, the report is the largest known national analysis of medication errors related to surgery, Ms. Cousins said at the briefing.

The findings were also provided in a briefing to 11 national organizations and agencies, with the intention of calling them to action and to “mobilize not only the organizations but their membership to develop risk-prevention strategies that will make their patient care safer,” Ms. Cousins said.

The 47 recommendations issued in the report include implementing strategies that improve communication among all perioperative team members, designating a pharmacist to coordinate medication safety, and working to ensure that medications are administered on time.

The report is available (for purchase) at www.usp.org/products/medMarx

The maker of rosiglitazone is notifying health care professionals about an increased rate of fractures found in women participating in two large, long-term controlled trials of the drug, and the company is advising providers to consider these findings when prescribing rosiglitazone.

In a letter to health care professionals posted on the Food and Drug Administration's MedWatch site, GlaxoSmithKline notes that in ADOPT (A Diabetes Outcome and Progression Trial), significantly more women who received rosiglitazone monotherapy had fractures, compared with women who received metformin or glyburide.

ADOPT, a randomized, double-blind parallel group study of 4,360 recently diagnosed type 2 diabetic patients, compared glycemic control with rosiglitazone to metformin and glyburide monotherapies over 4–6 years, and was published last year (N. Engl. J. Med. 2006;355:2427–43). The trial showed that rosiglitazone monotherapy was associated with a lower treatment failure rate at 5 years than was either metformin or glyburide.

In addition, a preliminary review of interim fracture data in another large, ongoing, long-term controlled rosiglitazone study was “reported to [GlaxoSmithKline] as being consistent with the observations from ADOPT,” the letter said. The review was conducted by an independent safety committee at GlaxoSmithKline's request. The committee has recommended that the study, which is looking at cardiovascular end points in patients with type 2 diabetes, continue with no modifications; final results are expected to be available in 2009.

In ADOPT, about 9% of the women on rosiglitazone experienced a fracture during the course of the study, for a rate of 2.74 fractures per 100 patient-years. This was significantly higher than the 5% of women on metformin and 3.5% of women on glyburide who experienced a fracture, for 1.5 fractures and 1.3 fractures per 100 patient-years, respectively.

Most of the fractures among the women on rosiglitazone were in the humerus, hand, or foot, which are different from the fracture sites associated with postmenopausal osteoporosis. The number of women with a hip or spine fracture—the kind typically associated with postmenopausal osteoporosis—“was low and similar among the three treatment groups,” according to the letter, which was signed by Dr. Alexander R. Cobitz, senior director, metabolism, in clinical development and medical affairs at GlaxoSmithKline.

The incidence of fractures among the men in the study was similar in all three treatment groups.

“Presently, our understanding of the clinical significance of the findings from these two long-term trials is incomplete,” the letter said. For now, the company “believes the risk of fracture should be considered in the care of patients, especially female patients, with type 2 diabetes mellitus who are currently being treated with rosiglitazone, or when initiation of rosiglitazone treatment is being considered.”

Rosiglitazone, approved by the FDA in 1999, is marketed as Avandia and is also available in combination with metformin (Avandamet) and with glimepiride (Avandaryl) for treating type 2 diabetes.

Read the letter at www.fda.gov/medwatch/safety/2007/Avandia_GSK_Ltr.pdfwww.fda.gov/medwatch

The maker of rosiglitazone is notifying health care professionals about an increased rate of fractures found in women participating in two large, long-term controlled trials of the drug, and the company is advising providers to consider these findings when prescribing rosiglitazone.

In a letter to health care professionals posted on the Food and Drug Administration's MedWatch site, GlaxoSmithKline notes that in ADOPT (A Diabetes Outcome and Progression Trial), significantly more women who received rosiglitazone monotherapy had fractures, compared with women who received metformin or glyburide.

ADOPT, a randomized, double-blind parallel group study of 4,360 recently diagnosed type 2 diabetic patients, compared glycemic control with rosiglitazone to metformin and glyburide monotherapies over 4–6 years, and was published last year (N. Engl. J. Med. 2006;355:2427–43). The trial showed that rosiglitazone monotherapy was associated with a lower treatment failure rate at 5 years than was either metformin or glyburide.

In addition, a preliminary review of interim fracture data in another large, ongoing, long-term controlled rosiglitazone study was “reported to [GlaxoSmithKline] as being consistent with the observations from ADOPT,” the letter said. The review was conducted by an independent safety committee at GlaxoSmithKline's request. The committee has recommended that the study, which is looking at cardiovascular end points in patients with type 2 diabetes, continue with no modifications; final results are expected to be available in 2009.

In ADOPT, about 9% of the women on rosiglitazone experienced a fracture during the course of the study, for a rate of 2.74 fractures per 100 patient-years. This was significantly higher than the 5% of women on metformin and 3.5% of women on glyburide who experienced a fracture, for 1.5 fractures and 1.3 fractures per 100 patient-years, respectively.

Most of the fractures among the women on rosiglitazone were in the humerus, hand, or foot, which are different from the fracture sites associated with postmenopausal osteoporosis. The number of women with a hip or spine fracture—the kind typically associated with postmenopausal osteoporosis—“was low and similar among the three treatment groups,” according to the letter, which was signed by Dr. Alexander R. Cobitz, senior director, metabolism, in clinical development and medical affairs at GlaxoSmithKline.

The incidence of fractures among the men in the study was similar in all three treatment groups.

“Presently, our understanding of the clinical significance of the findings from these two long-term trials is incomplete,” the letter said. For now, the company “believes the risk of fracture should be considered in the care of patients, especially female patients, with type 2 diabetes mellitus who are currently being treated with rosiglitazone, or when initiation of rosiglitazone treatment is being considered.”

Rosiglitazone, approved by the FDA in 1999, is marketed as Avandia and is also available in combination with metformin (Avandamet) and with glimepiride (Avandaryl) for treating type 2 diabetes.

Read the letter at www.fda.gov/medwatch/safety/2007/Avandia_GSK_Ltr.pdfwww.fda.gov/medwatch

The maker of rosiglitazone is notifying health care professionals about an increased rate of fractures found in women participating in two large, long-term controlled trials of the drug, and the company is advising providers to consider these findings when prescribing rosiglitazone.

In a letter to health care professionals posted on the Food and Drug Administration's MedWatch site, GlaxoSmithKline notes that in ADOPT (A Diabetes Outcome and Progression Trial), significantly more women who received rosiglitazone monotherapy had fractures, compared with women who received metformin or glyburide.

ADOPT, a randomized, double-blind parallel group study of 4,360 recently diagnosed type 2 diabetic patients, compared glycemic control with rosiglitazone to metformin and glyburide monotherapies over 4–6 years, and was published last year (N. Engl. J. Med. 2006;355:2427–43). The trial showed that rosiglitazone monotherapy was associated with a lower treatment failure rate at 5 years than was either metformin or glyburide.

In addition, a preliminary review of interim fracture data in another large, ongoing, long-term controlled rosiglitazone study was “reported to [GlaxoSmithKline] as being consistent with the observations from ADOPT,” the letter said. The review was conducted by an independent safety committee at GlaxoSmithKline's request. The committee has recommended that the study, which is looking at cardiovascular end points in patients with type 2 diabetes, continue with no modifications; final results are expected to be available in 2009.

In ADOPT, about 9% of the women on rosiglitazone experienced a fracture during the course of the study, for a rate of 2.74 fractures per 100 patient-years. This was significantly higher than the 5% of women on metformin and 3.5% of women on glyburide who experienced a fracture, for 1.5 fractures and 1.3 fractures per 100 patient-years, respectively.

Most of the fractures among the women on rosiglitazone were in the humerus, hand, or foot, which are different from the fracture sites associated with postmenopausal osteoporosis. The number of women with a hip or spine fracture—the kind typically associated with postmenopausal osteoporosis—“was low and similar among the three treatment groups,” according to the letter, which was signed by Dr. Alexander R. Cobitz, senior director, metabolism, in clinical development and medical affairs at GlaxoSmithKline.

The incidence of fractures among the men in the study was similar in all three treatment groups.

“Presently, our understanding of the clinical significance of the findings from these two long-term trials is incomplete,” the letter said. For now, the company “believes the risk of fracture should be considered in the care of patients, especially female patients, with type 2 diabetes mellitus who are currently being treated with rosiglitazone, or when initiation of rosiglitazone treatment is being considered.”

Rosiglitazone, approved by the FDA in 1999, is marketed as Avandia and is also available in combination with metformin (Avandamet) and with glimepiride (Avandaryl) for treating type 2 diabetes.

Read the letter at www.fda.gov/medwatch/safety/2007/Avandia_GSK_Ltr.pdfwww.fda.gov/medwatch

The Food and Drug Administration has upgraded the pregnancy risk category for NovoLog insulin from category C to B, based on the results of a large multinational study of pregnant women with type 1 diabetes.

The change was announced by the manufacturer, Novo Nordisk, early this year. NovoLog is the trade name for insulin aspart (rDNA origin) injection, a rapid acting insulin analogue that was approved by the FDA in 2000.

The study, conducted at 63 sites in 18 countries, compared NovoLog with regular human insulin in 322 pregnant women with type 1 diabetes. The study found that changes in HbA_1c and the rate of maternal hypoglycemia were comparable in both groups, according to the company. The study was too small to make any conclusions about the risk of congenital malformations associated with NovoLog, according to a statement issued by Novo Nordisk.

The study also found that there was a reduced risk of neonatal hypoglycemia (glucose below 2.6 mmol/L) requiring treatment and “consistently low rates” of major maternal hypoglycemia and fewer preterm deliveries among the women treated with NovoLog, compared with those treated with regular human insulin.

Dr. Gideon Koren, director of the Motherisk Program, a teratogen information service at the Hospital for Sick Children, Toronto, said that he was pleased to see a decision based on a large, well-designed study. “This is more the exception than the rule, because very few such studies are being conducted and reported in pregnancy,” he noted in an interview.

“Insulin, being a very large molecule, is not expected to cross the human placenta, as was shown for regular insulin numerous times, and by us recently for insulin lispro,” added Dr. Koren, professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto.

Lispro, marketed by Eli Lilly as Humalog, is another rapid-acting human insulin analogue and is classified as pregnancy category B. The drug's label states that there are no adequate well-controlled studies in pregnant women, and that because animal reproduction studies “are not always predictive of human response,” the drug should be used during pregnancy only if clearly needed.

Gerald G. Briggs, B. Pharm., pharmacist clinical specialist, Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., noted in an interview that both insulin analogues are commonly used in pregnancy, but are usually reserved for type 1 diabetics, particularly those whose diabetes is considered difficult to control. He considers all insulins—human, pork, analogues, as well as inhaled insulin—as category B drugs, even though some are classified as C. All are large molecules that are closely related to human insulin and it is unlikely that insulin crosses the placenta, at least in clinically significant amounts, said Mr. Briggs, coauthor of the reference book “Drugs in Pregnancy and Lactation.”

A third insulin analogue on the market, insulin glulisine (Apidra), approved in 2004, has a pharmacokinetic profile that is similar to insulin aspart and lispro. Its label says that the effect of pregnancy on the drug's pharmacokinetics and pharmacodynamics has not been studied.

Under the current system of pregnancy risk categories used by the Food and Drug Administration, a drug is classified in category B if animal studies show no risk or human data are reassuring. A drug is classified as category C when animal studies have demonstrated adverse effects on the fetus, or have not been done, and studies in women are not available.

The Food and Drug Administration has upgraded the pregnancy risk category for NovoLog insulin from category C to B, based on the results of a large multinational study of pregnant women with type 1 diabetes.

The change was announced by the manufacturer, Novo Nordisk, early this year. NovoLog is the trade name for insulin aspart (rDNA origin) injection, a rapid acting insulin analogue that was approved by the FDA in 2000.

The study, conducted at 63 sites in 18 countries, compared NovoLog with regular human insulin in 322 pregnant women with type 1 diabetes. The study found that changes in HbA_1c and the rate of maternal hypoglycemia were comparable in both groups, according to the company. The study was too small to make any conclusions about the risk of congenital malformations associated with NovoLog, according to a statement issued by Novo Nordisk.

The study also found that there was a reduced risk of neonatal hypoglycemia (glucose below 2.6 mmol/L) requiring treatment and “consistently low rates” of major maternal hypoglycemia and fewer preterm deliveries among the women treated with NovoLog, compared with those treated with regular human insulin.

Dr. Gideon Koren, director of the Motherisk Program, a teratogen information service at the Hospital for Sick Children, Toronto, said that he was pleased to see a decision based on a large, well-designed study. “This is more the exception than the rule, because very few such studies are being conducted and reported in pregnancy,” he noted in an interview.

“Insulin, being a very large molecule, is not expected to cross the human placenta, as was shown for regular insulin numerous times, and by us recently for insulin lispro,” added Dr. Koren, professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto.

Lispro, marketed by Eli Lilly as Humalog, is another rapid-acting human insulin analogue and is classified as pregnancy category B. The drug's label states that there are no adequate well-controlled studies in pregnant women, and that because animal reproduction studies “are not always predictive of human response,” the drug should be used during pregnancy only if clearly needed.

Gerald G. Briggs, B. Pharm., pharmacist clinical specialist, Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., noted in an interview that both insulin analogues are commonly used in pregnancy, but are usually reserved for type 1 diabetics, particularly those whose diabetes is considered difficult to control. He considers all insulins—human, pork, analogues, as well as inhaled insulin—as category B drugs, even though some are classified as C. All are large molecules that are closely related to human insulin and it is unlikely that insulin crosses the placenta, at least in clinically significant amounts, said Mr. Briggs, coauthor of the reference book “Drugs in Pregnancy and Lactation.”

A third insulin analogue on the market, insulin glulisine (Apidra), approved in 2004, has a pharmacokinetic profile that is similar to insulin aspart and lispro. Its label says that the effect of pregnancy on the drug's pharmacokinetics and pharmacodynamics has not been studied.

Under the current system of pregnancy risk categories used by the Food and Drug Administration, a drug is classified in category B if animal studies show no risk or human data are reassuring. A drug is classified as category C when animal studies have demonstrated adverse effects on the fetus, or have not been done, and studies in women are not available.

The Food and Drug Administration has upgraded the pregnancy risk category for NovoLog insulin from category C to B, based on the results of a large multinational study of pregnant women with type 1 diabetes.

The change was announced by the manufacturer, Novo Nordisk, early this year. NovoLog is the trade name for insulin aspart (rDNA origin) injection, a rapid acting insulin analogue that was approved by the FDA in 2000.

The study, conducted at 63 sites in 18 countries, compared NovoLog with regular human insulin in 322 pregnant women with type 1 diabetes. The study found that changes in HbA_1c and the rate of maternal hypoglycemia were comparable in both groups, according to the company. The study was too small to make any conclusions about the risk of congenital malformations associated with NovoLog, according to a statement issued by Novo Nordisk.

The study also found that there was a reduced risk of neonatal hypoglycemia (glucose below 2.6 mmol/L) requiring treatment and “consistently low rates” of major maternal hypoglycemia and fewer preterm deliveries among the women treated with NovoLog, compared with those treated with regular human insulin.

Dr. Gideon Koren, director of the Motherisk Program, a teratogen information service at the Hospital for Sick Children, Toronto, said that he was pleased to see a decision based on a large, well-designed study. “This is more the exception than the rule, because very few such studies are being conducted and reported in pregnancy,” he noted in an interview.

“Insulin, being a very large molecule, is not expected to cross the human placenta, as was shown for regular insulin numerous times, and by us recently for insulin lispro,” added Dr. Koren, professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto.

Lispro, marketed by Eli Lilly as Humalog, is another rapid-acting human insulin analogue and is classified as pregnancy category B. The drug's label states that there are no adequate well-controlled studies in pregnant women, and that because animal reproduction studies “are not always predictive of human response,” the drug should be used during pregnancy only if clearly needed.

Gerald G. Briggs, B. Pharm., pharmacist clinical specialist, Women's Pavilion, Miller Children's Hospital, Long Beach, Calif., noted in an interview that both insulin analogues are commonly used in pregnancy, but are usually reserved for type 1 diabetics, particularly those whose diabetes is considered difficult to control. He considers all insulins—human, pork, analogues, as well as inhaled insulin—as category B drugs, even though some are classified as C. All are large molecules that are closely related to human insulin and it is unlikely that insulin crosses the placenta, at least in clinically significant amounts, said Mr. Briggs, coauthor of the reference book “Drugs in Pregnancy and Lactation.”

A third insulin analogue on the market, insulin glulisine (Apidra), approved in 2004, has a pharmacokinetic profile that is similar to insulin aspart and lispro. Its label says that the effect of pregnancy on the drug's pharmacokinetics and pharmacodynamics has not been studied.

Under the current system of pregnancy risk categories used by the Food and Drug Administration, a drug is classified in category B if animal studies show no risk or human data are reassuring. A drug is classified as category C when animal studies have demonstrated adverse effects on the fetus, or have not been done, and studies in women are not available.

The Food and Drug Administration is advising health care providers to stop using two models of a machine used to wash and disinfect flexible endoscopes, if the providers have an alternative method of disinfection.

The machines are the System 83 Plus Washer/Disinfector and the System Plus 83 Mini-flex Washer/Disinfector, which are manufactured by Custom Ultrasonics Inc. A statement issued by the FDA on Feb. 7 says that the agency and company signed a consent decree of permanent injunction, in which the company agreed to stop manufacturing and distributing the machines until it brings its methods and controls used to manufacture the machines into compliance with FDA's good manufacturing requirements. The company also agreed to develop and implement adequate written medical device reporting procedures, according to the statement.

The FDA is not aware of any adverse events resulting from this problem, the statement says, but adds that a potential health hazard exists because improperly cleaned and disinfected endoscopes “can be a source of transmission of pathogens between patients, causing life-threatening infections.”

The agency advised health care providers who use the machines to stop using them if they have other options, including using another device or “following appropriate protocols to manually wash and disinfect the device.” If they have no alternative, they “should carefully weigh the risks and benefits of using these products,” the FDA said.

In a letter to customers dated Feb. 8 and posted on the company's Web site, Custom Ultrasonics said that it was cooperating with the FDA and expected to be in compliance with the FDA's regulations and have the matter resolved “very shortly.”

The letter stressed that the company was not aware of any reports of an infection or disease transmission associated with the proper use of the System 83 Plus, and that it was safe and effective for cleaning and high-level disinfection of flexible endoscopes “when used in accordance with its labeling.” The System 83 Plus machines have been used to reprocess several million flexible endoscopes over the past 20 years, according to the letter.

The Food and Drug Administration is advising health care providers to stop using two models of a machine used to wash and disinfect flexible endoscopes, if the providers have an alternative method of disinfection.

The machines are the System 83 Plus Washer/Disinfector and the System Plus 83 Mini-flex Washer/Disinfector, which are manufactured by Custom Ultrasonics Inc. A statement issued by the FDA on Feb. 7 says that the agency and company signed a consent decree of permanent injunction, in which the company agreed to stop manufacturing and distributing the machines until it brings its methods and controls used to manufacture the machines into compliance with FDA's good manufacturing requirements. The company also agreed to develop and implement adequate written medical device reporting procedures, according to the statement.

The FDA is not aware of any adverse events resulting from this problem, the statement says, but adds that a potential health hazard exists because improperly cleaned and disinfected endoscopes “can be a source of transmission of pathogens between patients, causing life-threatening infections.”

The agency advised health care providers who use the machines to stop using them if they have other options, including using another device or “following appropriate protocols to manually wash and disinfect the device.” If they have no alternative, they “should carefully weigh the risks and benefits of using these products,” the FDA said.

In a letter to customers dated Feb. 8 and posted on the company's Web site, Custom Ultrasonics said that it was cooperating with the FDA and expected to be in compliance with the FDA's regulations and have the matter resolved “very shortly.”

The letter stressed that the company was not aware of any reports of an infection or disease transmission associated with the proper use of the System 83 Plus, and that it was safe and effective for cleaning and high-level disinfection of flexible endoscopes “when used in accordance with its labeling.” The System 83 Plus machines have been used to reprocess several million flexible endoscopes over the past 20 years, according to the letter.

The Food and Drug Administration is advising health care providers to stop using two models of a machine used to wash and disinfect flexible endoscopes, if the providers have an alternative method of disinfection.

The machines are the System 83 Plus Washer/Disinfector and the System Plus 83 Mini-flex Washer/Disinfector, which are manufactured by Custom Ultrasonics Inc. A statement issued by the FDA on Feb. 7 says that the agency and company signed a consent decree of permanent injunction, in which the company agreed to stop manufacturing and distributing the machines until it brings its methods and controls used to manufacture the machines into compliance with FDA's good manufacturing requirements. The company also agreed to develop and implement adequate written medical device reporting procedures, according to the statement.

The FDA is not aware of any adverse events resulting from this problem, the statement says, but adds that a potential health hazard exists because improperly cleaned and disinfected endoscopes “can be a source of transmission of pathogens between patients, causing life-threatening infections.”

The agency advised health care providers who use the machines to stop using them if they have other options, including using another device or “following appropriate protocols to manually wash and disinfect the device.” If they have no alternative, they “should carefully weigh the risks and benefits of using these products,” the FDA said.

In a letter to customers dated Feb. 8 and posted on the company's Web site, Custom Ultrasonics said that it was cooperating with the FDA and expected to be in compliance with the FDA's regulations and have the matter resolved “very shortly.”

The letter stressed that the company was not aware of any reports of an infection or disease transmission associated with the proper use of the System 83 Plus, and that it was safe and effective for cleaning and high-level disinfection of flexible endoscopes “when used in accordance with its labeling.” The System 83 Plus machines have been used to reprocess several million flexible endoscopes over the past 20 years, according to the letter.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

The Food and Drug Administration has reissued its warning that buying prescription drugs online can be dangerous after preliminary tests detected haloperidol in certain drugs purchased over the Internet.

Preliminary analyses determined that some orders of zolpidem (Ambien), alprazolam (Xanax), escitalopram (Lexapro), and lorazepam (Ativan), obtained by U.S. consumers over the Internet, actually contained the antipsychotic drug haloperidol (Haldol), the agency said in a statement. The statement refers to reports of people who've had emergency medical treatment for symptoms such as muscle spasms, difficulty breathing, and muscle stiffness after taking the pills.

Although the affected consumers named several Web sites through which the products were purchased, identifying the vendors “is difficult because of the deceptive practices of many commercial outlets on the Internet,” according to the statement. The packages containing these products were postmarked in Greece, but that may not be where they originated. The investigation is continuing, the statement said.

Photographs of the tablets that contained haloperidol are available at www.fda.gov/bbs/topics/news/photos/haloperidol.htmlwww.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

Information on buying medication online is provided at www.fda.gov/buyonline

The Food and Drug Administration has reissued its warning that buying prescription drugs online can be dangerous after preliminary tests detected haloperidol in certain drugs purchased over the Internet.

Preliminary analyses determined that some orders of zolpidem (Ambien), alprazolam (Xanax), escitalopram (Lexapro), and lorazepam (Ativan), obtained by U.S. consumers over the Internet, actually contained the antipsychotic drug haloperidol (Haldol), the agency said in a statement. The statement refers to reports of people who've had emergency medical treatment for symptoms such as muscle spasms, difficulty breathing, and muscle stiffness after taking the pills.

Although the affected consumers named several Web sites through which the products were purchased, identifying the vendors “is difficult because of the deceptive practices of many commercial outlets on the Internet,” according to the statement. The packages containing these products were postmarked in Greece, but that may not be where they originated. The investigation is continuing, the statement said.

Photographs of the tablets that contained haloperidol are available at www.fda.gov/bbs/topics/news/photos/haloperidol.htmlwww.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

Information on buying medication online is provided at www.fda.gov/buyonline

The Food and Drug Administration has reissued its warning that buying prescription drugs online can be dangerous after preliminary tests detected haloperidol in certain drugs purchased over the Internet.

Preliminary analyses determined that some orders of zolpidem (Ambien), alprazolam (Xanax), escitalopram (Lexapro), and lorazepam (Ativan), obtained by U.S. consumers over the Internet, actually contained the antipsychotic drug haloperidol (Haldol), the agency said in a statement. The statement refers to reports of people who've had emergency medical treatment for symptoms such as muscle spasms, difficulty breathing, and muscle stiffness after taking the pills.

Although the affected consumers named several Web sites through which the products were purchased, identifying the vendors “is difficult because of the deceptive practices of many commercial outlets on the Internet,” according to the statement. The packages containing these products were postmarked in Greece, but that may not be where they originated. The investigation is continuing, the statement said.

Photographs of the tablets that contained haloperidol are available at www.fda.gov/bbs/topics/news/photos/haloperidol.htmlwww.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

Information on buying medication online is provided at www.fda.gov/buyonline

The Food and Drug Administration has eliminated two indications for the antibiotic telithromycin and added a black box warning to its label stating the drug is contraindicated in people with myasthenia gravis.

Telithromycin, which is marketed by Sanofi-Aventis as Ketek, is no longer approved to treat acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.

“FDA has determined that the balance of benefits and risks for Ketek do not support continued approval of Ketek for these generally nonserious and often self-limited illnesses,” Dr. John Jenkins, director of the FDA's Office of New Drugs, said Feb. 12 in a telebriefing that was held to announce the revisions.

The ketolide antibiotic remains approved for treatment of mild to moderate community-acquired pneumonia (CAP) in patients aged 18 and over. The label now includes a black box warning and contraindication about the risks of telithromycin in those with myasthenia gravis. Reports have included life-threatening respiratory failure associated with use of the drug in this population.

The warnings section of the drug's label was also updated to include more information about other drug-specific adverse events, including visual disturbances and loss of consciousness.

A bolded warning regarding the risk of potentially fatal hepatotoxicity, which was added in June 2006, will remain unchanged.

In addition, an FDA-approved patient medication guide, developed with the manufacturer, now must be distributed with prescriptions and refills of telithromycin.

Although the evidence for a favorable risk-benefit profile is weak for the sinusitis and bronchitis indications, “community-acquired pneumonia kills people,” commented Dr. John Bartlett, professor of medicine at Johns Hopkins University, Baltimore. “And Ketek does have a clear advantage in the sense that it is highly effective, at least in the test tube, against the most resistant pneumococci, the most common cause of pneumonia,” he said in an interview.

Dr. Bartlett was a member of the committee that developed guidelines on the management of CAP in adults that were released by the Infectious Diseases Society of America and the American Thoracic Society shortly before the FDA's decision was announced. (See The Effective Physician column on this page.) Referring to postmarketing reports of life-threatening hepatotoxicity associated with telithromycin, the guidelines note that the committee “is awaiting further evaluation of the safety of this drug by the FDA before making its final recommendation” regarding the drug's role in treating CAP (Clin. Infect. Dis. 2007;44 [Suppl 2]:S27-72).

The label revisions reflect recommendations made at a joint Anti-Infective Drugs and Drug Safety and Risk Management Advisory Committee meeting in December 2006, where the majority of the two panels recommended that based on the available data, including data collected since the drug was approved in 2004, the benefits of telithromycin did not outweigh its risks for the sinusitis and bronchitis indications. Panelists indicated, however, that the drug's benefits outweighed its risks in patients with CAP.

The panel also recommended the patient medication guide and the boxed warning regarding risk in myasthenia gravis patients.

At the December meeting, the FDA reported that there had been 33 reports of exacerbations of the neurologic disease associated with telithromycin since 2004. These cases included 7 that were life-threatening and 12 in which patients required a ventilator or intubation.

Also during the meeting, the FDA reported there were 12 cases of acute liver failure among 5 million U.S. prescriptions written from 2004 to 2006, resulting in a reporting rate of 23 per 10 million prescriptions.

During the telebriefing, Dr. Gerald Del Pan, director of the FDA's Office of Surveillance and Epidemiology, in the Center for Drug Evaluation and Research, said that since the December meeting, the agency had received one additional report of a patient with liver complications associated with telithromycin. The complications do not appear to have been fatal, and the agency is investigating this case further.

Sanofi-Aventis will provide information on the revisions to health care professionals in a letter to health care providers, and have internal medical experts available to answer questions form health care professionals, by calling 800-633-1610 (option 1).

For more information, visit www.fda.gov/cder/drug/infopage/telithromycin/default.htmwww.sanofi-aventis.us/live/us/en/index.jsp.

The Food and Drug Administration has eliminated two indications for the antibiotic telithromycin and added a black box warning to its label stating the drug is contraindicated in people with myasthenia gravis.

Telithromycin, which is marketed by Sanofi-Aventis as Ketek, is no longer approved to treat acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.

“FDA has determined that the balance of benefits and risks for Ketek do not support continued approval of Ketek for these generally nonserious and often self-limited illnesses,” Dr. John Jenkins, director of the FDA's Office of New Drugs, said Feb. 12 in a telebriefing that was held to announce the revisions.

The ketolide antibiotic remains approved for treatment of mild to moderate community-acquired pneumonia (CAP) in patients aged 18 and over. The label now includes a black box warning and contraindication about the risks of telithromycin in those with myasthenia gravis. Reports have included life-threatening respiratory failure associated with use of the drug in this population.

The warnings section of the drug's label was also updated to include more information about other drug-specific adverse events, including visual disturbances and loss of consciousness.

A bolded warning regarding the risk of potentially fatal hepatotoxicity, which was added in June 2006, will remain unchanged.

In addition, an FDA-approved patient medication guide, developed with the manufacturer, now must be distributed with prescriptions and refills of telithromycin.

Although the evidence for a favorable risk-benefit profile is weak for the sinusitis and bronchitis indications, “community-acquired pneumonia kills people,” commented Dr. John Bartlett, professor of medicine at Johns Hopkins University, Baltimore. “And Ketek does have a clear advantage in the sense that it is highly effective, at least in the test tube, against the most resistant pneumococci, the most common cause of pneumonia,” he said in an interview.

Dr. Bartlett was a member of the committee that developed guidelines on the management of CAP in adults that were released by the Infectious Diseases Society of America and the American Thoracic Society shortly before the FDA's decision was announced. (See The Effective Physician column on this page.) Referring to postmarketing reports of life-threatening hepatotoxicity associated with telithromycin, the guidelines note that the committee “is awaiting further evaluation of the safety of this drug by the FDA before making its final recommendation” regarding the drug's role in treating CAP (Clin. Infect. Dis. 2007;44 [Suppl 2]:S27-72).

The label revisions reflect recommendations made at a joint Anti-Infective Drugs and Drug Safety and Risk Management Advisory Committee meeting in December 2006, where the majority of the two panels recommended that based on the available data, including data collected since the drug was approved in 2004, the benefits of telithromycin did not outweigh its risks for the sinusitis and bronchitis indications. Panelists indicated, however, that the drug's benefits outweighed its risks in patients with CAP.

The panel also recommended the patient medication guide and the boxed warning regarding risk in myasthenia gravis patients.

At the December meeting, the FDA reported that there had been 33 reports of exacerbations of the neurologic disease associated with telithromycin since 2004. These cases included 7 that were life-threatening and 12 in which patients required a ventilator or intubation.

Also during the meeting, the FDA reported there were 12 cases of acute liver failure among 5 million U.S. prescriptions written from 2004 to 2006, resulting in a reporting rate of 23 per 10 million prescriptions.

During the telebriefing, Dr. Gerald Del Pan, director of the FDA's Office of Surveillance and Epidemiology, in the Center for Drug Evaluation and Research, said that since the December meeting, the agency had received one additional report of a patient with liver complications associated with telithromycin. The complications do not appear to have been fatal, and the agency is investigating this case further.

Sanofi-Aventis will provide information on the revisions to health care professionals in a letter to health care providers, and have internal medical experts available to answer questions form health care professionals, by calling 800-633-1610 (option 1).

For more information, visit www.fda.gov/cder/drug/infopage/telithromycin/default.htmwww.sanofi-aventis.us/live/us/en/index.jsp.

The Food and Drug Administration has eliminated two indications for the antibiotic telithromycin and added a black box warning to its label stating the drug is contraindicated in people with myasthenia gravis.

Telithromycin, which is marketed by Sanofi-Aventis as Ketek, is no longer approved to treat acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.

“FDA has determined that the balance of benefits and risks for Ketek do not support continued approval of Ketek for these generally nonserious and often self-limited illnesses,” Dr. John Jenkins, director of the FDA's Office of New Drugs, said Feb. 12 in a telebriefing that was held to announce the revisions.

The ketolide antibiotic remains approved for treatment of mild to moderate community-acquired pneumonia (CAP) in patients aged 18 and over. The label now includes a black box warning and contraindication about the risks of telithromycin in those with myasthenia gravis. Reports have included life-threatening respiratory failure associated with use of the drug in this population.

The warnings section of the drug's label was also updated to include more information about other drug-specific adverse events, including visual disturbances and loss of consciousness.

A bolded warning regarding the risk of potentially fatal hepatotoxicity, which was added in June 2006, will remain unchanged.

In addition, an FDA-approved patient medication guide, developed with the manufacturer, now must be distributed with prescriptions and refills of telithromycin.

Although the evidence for a favorable risk-benefit profile is weak for the sinusitis and bronchitis indications, “community-acquired pneumonia kills people,” commented Dr. John Bartlett, professor of medicine at Johns Hopkins University, Baltimore. “And Ketek does have a clear advantage in the sense that it is highly effective, at least in the test tube, against the most resistant pneumococci, the most common cause of pneumonia,” he said in an interview.

Dr. Bartlett was a member of the committee that developed guidelines on the management of CAP in adults that were released by the Infectious Diseases Society of America and the American Thoracic Society shortly before the FDA's decision was announced. (See The Effective Physician column on this page.) Referring to postmarketing reports of life-threatening hepatotoxicity associated with telithromycin, the guidelines note that the committee “is awaiting further evaluation of the safety of this drug by the FDA before making its final recommendation” regarding the drug's role in treating CAP (Clin. Infect. Dis. 2007;44 [Suppl 2]:S27-72).

The label revisions reflect recommendations made at a joint Anti-Infective Drugs and Drug Safety and Risk Management Advisory Committee meeting in December 2006, where the majority of the two panels recommended that based on the available data, including data collected since the drug was approved in 2004, the benefits of telithromycin did not outweigh its risks for the sinusitis and bronchitis indications. Panelists indicated, however, that the drug's benefits outweighed its risks in patients with CAP.

The panel also recommended the patient medication guide and the boxed warning regarding risk in myasthenia gravis patients.

At the December meeting, the FDA reported that there had been 33 reports of exacerbations of the neurologic disease associated with telithromycin since 2004. These cases included 7 that were life-threatening and 12 in which patients required a ventilator or intubation.

Also during the meeting, the FDA reported there were 12 cases of acute liver failure among 5 million U.S. prescriptions written from 2004 to 2006, resulting in a reporting rate of 23 per 10 million prescriptions.

During the telebriefing, Dr. Gerald Del Pan, director of the FDA's Office of Surveillance and Epidemiology, in the Center for Drug Evaluation and Research, said that since the December meeting, the agency had received one additional report of a patient with liver complications associated with telithromycin. The complications do not appear to have been fatal, and the agency is investigating this case further.

Sanofi-Aventis will provide information on the revisions to health care professionals in a letter to health care providers, and have internal medical experts available to answer questions form health care professionals, by calling 800-633-1610 (option 1).

For more information, visit www.fda.gov/cder/drug/infopage/telithromycin/default.htmwww.sanofi-aventis.us/live/us/en/index.jsp.

The American Heart Association's new evidence-based guidelines for preventing cardiovascular disease in women emphasize a woman's lifetime risk and provide new recommendations on aspirin, folic acid, antioxidant therapy, and hormone therapy.

The updated guidelines are the most current clinical recommendations for preventing cardiovascular disease (CVD) in women aged 20 and older, addressing the primary and secondary prevention of chronic atherosclerotic vascular diseases. The recommendations are based on “a systematic search of the highest quality science, interpreted by experts in the fields of cardiology, epidemiology, family medicine, gynecology, internal medicine, neurology, nursing, public health, statistics, and surgery,” according to the authors, an expert panel. The guidelines will be published in the March 20 issue of Circulation.

The new guidelines place a greater emphasis on a woman's lifetime risk of CVD, rather than on the short-term risk, as in the previous guidelines, issued in 2004. The panel acknowledged that nearly all women are at risk for CVD, a fact that “underscores the importance of a heart-healthy lifestyle.” Instead of classifying a woman as being at high, intermediate, lower, or optimal risk, the 2007 guidelines recommend classifying a woman as high risk, at risk, or optimal risk.

Part of the rationale for emphasizing lifetime risk rather than short-term risk is evidence that physicians do not make strong lifestyle recommendations for women considered low risk, said Dr. Lori Mosca, the chair of the expert panel that wrote the new guidelines. Helping women understand—even though their short-term risk may not be impressive—that because heart disease and stroke are such common conditions, “many risk factors can be prevented by doctors [if they stress] a more aggressive lifestyle [intervention] early on,” she said in an interview, noting that 30% of women have CVD and almost one in three women dies of it.

For example, as women age, they tend to gain weight with every decade, increasing their risk for hypertension, abnormal cholesterol levels, and diabetes. “If we can communicate effectively with our patients that healthy lifestyles early on will prevent the development of risk factors requiring treatment … this may be very motivational for patients,” said Dr. Mosca, director of preventive cardiology at New York-Presbyterian Hospital.

She urged physicians to link positive behaviors with outcomes that are meaningful to the patient. “What doctors can do is help women understand that their behaviors now will make a difference even in their midlife, in terms of preventing risk factors, and later in life, preventing heart disease and stroke,” she said.

Other important differences from 2004 are the revisions regarding menopausal therapy, aspirin therapy, and folic acid, because more definitive data on these therapies have been published since that time. The guidelines state that hormone therapy and selective estrogen receptor modulation should not be used for primary or secondary prevention of CVD in women and that antioxidant supplements, such as β-carotene and vitamins E and C, should not be used. Folic acid, with or without vitamin B6 and B12 supplementation, should also not be used to prevent CVD.

More definitive clinical trial data are now available regarding the use of aspirin in women to prevent stroke, and the new guidelines say that “aspirin therapy should be considered for all women for stroke prevention, depending on the balance of risks and benefits.” This area is potentially a confusing one for physicians, Dr. Mosca said. The strengths of these recommendations are classified based on the levels of evidence available.

For high-risk women, aspirin therapy at 75-325 mg/day is recommended unless contraindicated, in which case clopidogrel should be substituted. The recommendation for aspirin for high-risk women—such as women with diabetes or heart disease—is class I, where the intervention is considered useful and effective and should be done unless there is a reason not to, Dr. Mosca said. For other at-risk or healthy women aged 65 and older, aspirin therapy at 81 or 100 mg every other day should be considered if their blood pressure is controlled “and benefit for ischemic stroke and MI prevention is likely to outweigh” the risk of GI bleeding and hemorrhagic stroke. This regimen should also be considered in women under age 65 when the benefit for preventing ischemic stroke is likely to outweigh the risks of treatment.

For women over 65, this is a class IIa, level B recommendation, where the intervention may prevent heart disease and stroke, but the benefits should outweigh the risks, she said. For women under 65, the evidence is very weak for stroke prevention. “It doesn't mean you can't do it … but for the majority of women under 65, the benefits of aspirin are not likely to outweigh the risks,” Dr. Mosca said in the interview. Routine use of aspirin in healthy women under age 65 should also not be used to prevent MI, with evidence that is class III. (The intervention is not useful or effective and may be harmful.)

An algorithm that health care providers can use to evaluate a woman's CVD risk and to prioritize preventive interventions is provided in the guidelines, as well as a list of the evidence-based clinical recommendations for preventing CVD in women, with lifestyle interventions, major risk factor interventions, and preventive drug interventions. Each recommendation also comes with the strength of the recommendation and the evidence used to support the recommendation. A table listing interventions that, based on current evidence, are not useful or effective and may be harmful for preventing CVD or MI in women is also incorporated.

The statement refers to a previous AHA study, which found that 36% of women did not perceive themselves to be at risk for CVD and 25% said their health care provider “did not say heart health was important.” And one in five “said their health care providers did not clearly explain how they could change their risk status.”

Other recommendations include advising women who need to lose weight or sustain weight loss to engage in moderate-intensity physical activity for 60-90 minutes on most but preferably all days of the week.

More research on the added benefits, risks, and costs of new CVD risk factors, such as high-sensitivity C-reactive protein, and new screening techniques, such as coronary calcium scoring, is needed before they can be incorporated into these guidelines, according to the panel.

Members of the panel represented organizations and cosponsors including the AHA, American College of Physicians, American College of Cardiology Foundation, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, and National Heart, Lung, and Blood Institute.

The American Heart Association's new evidence-based guidelines for preventing cardiovascular disease in women emphasize a woman's lifetime risk and provide new recommendations on aspirin, folic acid, antioxidant therapy, and hormone therapy.

The updated guidelines are the most current clinical recommendations for preventing cardiovascular disease (CVD) in women aged 20 and older, addressing the primary and secondary prevention of chronic atherosclerotic vascular diseases. The recommendations are based on “a systematic search of the highest quality science, interpreted by experts in the fields of cardiology, epidemiology, family medicine, gynecology, internal medicine, neurology, nursing, public health, statistics, and surgery,” according to the authors, an expert panel. The guidelines will be published in the March 20 issue of Circulation.

The new guidelines place a greater emphasis on a woman's lifetime risk of CVD, rather than on the short-term risk, as in the previous guidelines, issued in 2004. The panel acknowledged that nearly all women are at risk for CVD, a fact that “underscores the importance of a heart-healthy lifestyle.” Instead of classifying a woman as being at high, intermediate, lower, or optimal risk, the 2007 guidelines recommend classifying a woman as high risk, at risk, or optimal risk.

Part of the rationale for emphasizing lifetime risk rather than short-term risk is evidence that physicians do not make strong lifestyle recommendations for women considered low risk, said Dr. Lori Mosca, the chair of the expert panel that wrote the new guidelines. Helping women understand—even though their short-term risk may not be impressive—that because heart disease and stroke are such common conditions, “many risk factors can be prevented by doctors [if they stress] a more aggressive lifestyle [intervention] early on,” she said in an interview, noting that 30% of women have CVD and almost one in three women dies of it.

For example, as women age, they tend to gain weight with every decade, increasing their risk for hypertension, abnormal cholesterol levels, and diabetes. “If we can communicate effectively with our patients that healthy lifestyles early on will prevent the development of risk factors requiring treatment … this may be very motivational for patients,” said Dr. Mosca, director of preventive cardiology at New York-Presbyterian Hospital.

She urged physicians to link positive behaviors with outcomes that are meaningful to the patient. “What doctors can do is help women understand that their behaviors now will make a difference even in their midlife, in terms of preventing risk factors, and later in life, preventing heart disease and stroke,” she said.

Other important differences from 2004 are the revisions regarding menopausal therapy, aspirin therapy, and folic acid, because more definitive data on these therapies have been published since that time. The guidelines state that hormone therapy and selective estrogen receptor modulation should not be used for primary or secondary prevention of CVD in women and that antioxidant supplements, such as β-carotene and vitamins E and C, should not be used. Folic acid, with or without vitamin B6 and B12 supplementation, should also not be used to prevent CVD.

More definitive clinical trial data are now available regarding the use of aspirin in women to prevent stroke, and the new guidelines say that “aspirin therapy should be considered for all women for stroke prevention, depending on the balance of risks and benefits.” This area is potentially a confusing one for physicians, Dr. Mosca said. The strengths of these recommendations are classified based on the levels of evidence available.

For high-risk women, aspirin therapy at 75-325 mg/day is recommended unless contraindicated, in which case clopidogrel should be substituted. The recommendation for aspirin for high-risk women—such as women with diabetes or heart disease—is class I, where the intervention is considered useful and effective and should be done unless there is a reason not to, Dr. Mosca said. For other at-risk or healthy women aged 65 and older, aspirin therapy at 81 or 100 mg every other day should be considered if their blood pressure is controlled “and benefit for ischemic stroke and MI prevention is likely to outweigh” the risk of GI bleeding and hemorrhagic stroke. This regimen should also be considered in women under age 65 when the benefit for preventing ischemic stroke is likely to outweigh the risks of treatment.

For women over 65, this is a class IIa, level B recommendation, where the intervention may prevent heart disease and stroke, but the benefits should outweigh the risks, she said. For women under 65, the evidence is very weak for stroke prevention. “It doesn't mean you can't do it … but for the majority of women under 65, the benefits of aspirin are not likely to outweigh the risks,” Dr. Mosca said in the interview. Routine use of aspirin in healthy women under age 65 should also not be used to prevent MI, with evidence that is class III. (The intervention is not useful or effective and may be harmful.)

An algorithm that health care providers can use to evaluate a woman's CVD risk and to prioritize preventive interventions is provided in the guidelines, as well as a list of the evidence-based clinical recommendations for preventing CVD in women, with lifestyle interventions, major risk factor interventions, and preventive drug interventions. Each recommendation also comes with the strength of the recommendation and the evidence used to support the recommendation. A table listing interventions that, based on current evidence, are not useful or effective and may be harmful for preventing CVD or MI in women is also incorporated.

The statement refers to a previous AHA study, which found that 36% of women did not perceive themselves to be at risk for CVD and 25% said their health care provider “did not say heart health was important.” And one in five “said their health care providers did not clearly explain how they could change their risk status.”

Other recommendations include advising women who need to lose weight or sustain weight loss to engage in moderate-intensity physical activity for 60-90 minutes on most but preferably all days of the week.

More research on the added benefits, risks, and costs of new CVD risk factors, such as high-sensitivity C-reactive protein, and new screening techniques, such as coronary calcium scoring, is needed before they can be incorporated into these guidelines, according to the panel.

Members of the panel represented organizations and cosponsors including the AHA, American College of Physicians, American College of Cardiology Foundation, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, and National Heart, Lung, and Blood Institute.

The American Heart Association's new evidence-based guidelines for preventing cardiovascular disease in women emphasize a woman's lifetime risk and provide new recommendations on aspirin, folic acid, antioxidant therapy, and hormone therapy.

The updated guidelines are the most current clinical recommendations for preventing cardiovascular disease (CVD) in women aged 20 and older, addressing the primary and secondary prevention of chronic atherosclerotic vascular diseases. The recommendations are based on “a systematic search of the highest quality science, interpreted by experts in the fields of cardiology, epidemiology, family medicine, gynecology, internal medicine, neurology, nursing, public health, statistics, and surgery,” according to the authors, an expert panel. The guidelines will be published in the March 20 issue of Circulation.

The new guidelines place a greater emphasis on a woman's lifetime risk of CVD, rather than on the short-term risk, as in the previous guidelines, issued in 2004. The panel acknowledged that nearly all women are at risk for CVD, a fact that “underscores the importance of a heart-healthy lifestyle.” Instead of classifying a woman as being at high, intermediate, lower, or optimal risk, the 2007 guidelines recommend classifying a woman as high risk, at risk, or optimal risk.

Part of the rationale for emphasizing lifetime risk rather than short-term risk is evidence that physicians do not make strong lifestyle recommendations for women considered low risk, said Dr. Lori Mosca, the chair of the expert panel that wrote the new guidelines. Helping women understand—even though their short-term risk may not be impressive—that because heart disease and stroke are such common conditions, “many risk factors can be prevented by doctors [if they stress] a more aggressive lifestyle [intervention] early on,” she said in an interview, noting that 30% of women have CVD and almost one in three women dies of it.

For example, as women age, they tend to gain weight with every decade, increasing their risk for hypertension, abnormal cholesterol levels, and diabetes. “If we can communicate effectively with our patients that healthy lifestyles early on will prevent the development of risk factors requiring treatment … this may be very motivational for patients,” said Dr. Mosca, director of preventive cardiology at New York-Presbyterian Hospital.

She urged physicians to link positive behaviors with outcomes that are meaningful to the patient. “What doctors can do is help women understand that their behaviors now will make a difference even in their midlife, in terms of preventing risk factors, and later in life, preventing heart disease and stroke,” she said.

Other important differences from 2004 are the revisions regarding menopausal therapy, aspirin therapy, and folic acid, because more definitive data on these therapies have been published since that time. The guidelines state that hormone therapy and selective estrogen receptor modulation should not be used for primary or secondary prevention of CVD in women and that antioxidant supplements, such as β-carotene and vitamins E and C, should not be used. Folic acid, with or without vitamin B6 and B12 supplementation, should also not be used to prevent CVD.

More definitive clinical trial data are now available regarding the use of aspirin in women to prevent stroke, and the new guidelines say that “aspirin therapy should be considered for all women for stroke prevention, depending on the balance of risks and benefits.” This area is potentially a confusing one for physicians, Dr. Mosca said. The strengths of these recommendations are classified based on the levels of evidence available.

For high-risk women, aspirin therapy at 75-325 mg/day is recommended unless contraindicated, in which case clopidogrel should be substituted. The recommendation for aspirin for high-risk women—such as women with diabetes or heart disease—is class I, where the intervention is considered useful and effective and should be done unless there is a reason not to, Dr. Mosca said. For other at-risk or healthy women aged 65 and older, aspirin therapy at 81 or 100 mg every other day should be considered if their blood pressure is controlled “and benefit for ischemic stroke and MI prevention is likely to outweigh” the risk of GI bleeding and hemorrhagic stroke. This regimen should also be considered in women under age 65 when the benefit for preventing ischemic stroke is likely to outweigh the risks of treatment.

For women over 65, this is a class IIa, level B recommendation, where the intervention may prevent heart disease and stroke, but the benefits should outweigh the risks, she said. For women under 65, the evidence is very weak for stroke prevention. “It doesn't mean you can't do it … but for the majority of women under 65, the benefits of aspirin are not likely to outweigh the risks,” Dr. Mosca said in the interview. Routine use of aspirin in healthy women under age 65 should also not be used to prevent MI, with evidence that is class III. (The intervention is not useful or effective and may be harmful.)

An algorithm that health care providers can use to evaluate a woman's CVD risk and to prioritize preventive interventions is provided in the guidelines, as well as a list of the evidence-based clinical recommendations for preventing CVD in women, with lifestyle interventions, major risk factor interventions, and preventive drug interventions. Each recommendation also comes with the strength of the recommendation and the evidence used to support the recommendation. A table listing interventions that, based on current evidence, are not useful or effective and may be harmful for preventing CVD or MI in women is also incorporated.

The statement refers to a previous AHA study, which found that 36% of women did not perceive themselves to be at risk for CVD and 25% said their health care provider “did not say heart health was important.” And one in five “said their health care providers did not clearly explain how they could change their risk status.”

Other recommendations include advising women who need to lose weight or sustain weight loss to engage in moderate-intensity physical activity for 60-90 minutes on most but preferably all days of the week.

More research on the added benefits, risks, and costs of new CVD risk factors, such as high-sensitivity C-reactive protein, and new screening techniques, such as coronary calcium scoring, is needed before they can be incorporated into these guidelines, according to the panel.

Members of the panel represented organizations and cosponsors including the AHA, American College of Physicians, American College of Cardiology Foundation, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, and National Heart, Lung, and Blood Institute.

ROCKVILLE, MD. — Pediatric information in drug labels is expected to be easier to find and less confusing because of a new approach to incorporating pediatric information into the revised drug label design that is required for all new drugs approved since June last year.

At a meeting of the Food and Drug Administration's Pediatric Advisory Committee held to review pediatric adverse event reports for several drugs, Iris Masucci, Pharm.D., of the FDA's Center for Drug Evaluation and Research (CDER), provided an overview of the elements of the revised drug label.

A physician labeling rule implemented in June 2006 requires that drug labels be revised to make them more user friendly than the previous format. The label, or package insert, of any newly approved drug or biologic or supplemental efficacy approval of a drug submitted to the FDA after June 30, 2006, is required to be in the new format. Drugs approved in the 5 years before this implementation date are required to update their labeling to the new format according to a stepped timeline.

Drugs approved before that time are not required to make the change, but may do so voluntarily. The new labeling requirements also apply to biologics.

The approach on where to incorporate pediatric information into labels is a separate initiative from the new labeling format requirements. Rather, it is a more clearly defined paradigm than what has been used in the past, which will make labels more consistent in terms of how and where pediatric information is added, Dr. Masucci said in an interview.

A major change in the newly designed label is the highlights section, designed in response to feedback from physicians on what they wanted in a drug label, which appears at the beginning of the label. This is a half-page summary that provides the main information on a drug in a simple format with bullets and tables, Dr. Masucci said at the meeting.

This section includes the name of the product with the date of the initial U.S. approval; a boxed warning (if there is one); indications (which include the pharmacologic class of the drug); usage, dosage, and administration information; major changes recently made to the label; as well as dosage forms and strengths, contraindications, warning and precautions, adverse reactions, and drug interactions.

Also included is a patient counseling information statement and a section on use in specific populations, such as children.

The contents of the label include numbered sections with a specific number that corresponds to a particular section, which will be consistent for all drugs. For example, section 2 will always pertain to dosage and administration, and section 8 will always pertain to use in specific populations, which includes pediatric patients.

Other features of the new label include the consolidation of the warnings and precautions sections. Sections on drug interactions, use in specific populations, and patient counseling information—which appears in the precautions section in the old label—are now separate sections. Also, sections on clinical studies and nonclinical toxicology, previously optional, are now required, she said.

Contact information for the FDA's adverse event reporting program, MedWatch, and the drug's manufacturer for reporting adverse events are now also included in the label.

With the old format, it is difficult to determine if a drug is actually approved for pediatric use, Dr. Masucci said, noting that for example, in some tables, a pediatric dose may be listed but no pediatric data are listed.

If the new data are adequate to warrant a pediatric indication, the pediatric information is included in the applicable sections: indications and usage, dosage and administration, adverse reactions, use in specific populations, pharmacokinetics and pharmacodynamics, and clinical studies.

However, if the data are not adequate to support pediatric approval, all pediatric information on the drug appears in the section on “Use in specific populations-Pediatric Use,” which she said “will avoid the implication of approval.”

SOURCE: DR. MASUCCI/ELSEVIER GLOBAL MEDICAL NEWS

ROCKVILLE, MD. — Pediatric information in drug labels is expected to be easier to find and less confusing because of a new approach to incorporating pediatric information into the revised drug label design that is required for all new drugs approved since June last year.

At a meeting of the Food and Drug Administration's Pediatric Advisory Committee held to review pediatric adverse event reports for several drugs, Iris Masucci, Pharm.D., of the FDA's Center for Drug Evaluation and Research (CDER), provided an overview of the elements of the revised drug label.

A physician labeling rule implemented in June 2006 requires that drug labels be revised to make them more user friendly than the previous format. The label, or package insert, of any newly approved drug or biologic or supplemental efficacy approval of a drug submitted to the FDA after June 30, 2006, is required to be in the new format. Drugs approved in the 5 years before this implementation date are required to update their labeling to the new format according to a stepped timeline.

Drugs approved before that time are not required to make the change, but may do so voluntarily. The new labeling requirements also apply to biologics.

The approach on where to incorporate pediatric information into labels is a separate initiative from the new labeling format requirements. Rather, it is a more clearly defined paradigm than what has been used in the past, which will make labels more consistent in terms of how and where pediatric information is added, Dr. Masucci said in an interview.

A major change in the newly designed label is the highlights section, designed in response to feedback from physicians on what they wanted in a drug label, which appears at the beginning of the label. This is a half-page summary that provides the main information on a drug in a simple format with bullets and tables, Dr. Masucci said at the meeting.

This section includes the name of the product with the date of the initial U.S. approval; a boxed warning (if there is one); indications (which include the pharmacologic class of the drug); usage, dosage, and administration information; major changes recently made to the label; as well as dosage forms and strengths, contraindications, warning and precautions, adverse reactions, and drug interactions.

Also included is a patient counseling information statement and a section on use in specific populations, such as children.

The contents of the label include numbered sections with a specific number that corresponds to a particular section, which will be consistent for all drugs. For example, section 2 will always pertain to dosage and administration, and section 8 will always pertain to use in specific populations, which includes pediatric patients.

Other features of the new label include the consolidation of the warnings and precautions sections. Sections on drug interactions, use in specific populations, and patient counseling information—which appears in the precautions section in the old label—are now separate sections. Also, sections on clinical studies and nonclinical toxicology, previously optional, are now required, she said.

Contact information for the FDA's adverse event reporting program, MedWatch, and the drug's manufacturer for reporting adverse events are now also included in the label.

With the old format, it is difficult to determine if a drug is actually approved for pediatric use, Dr. Masucci said, noting that for example, in some tables, a pediatric dose may be listed but no pediatric data are listed.

If the new data are adequate to warrant a pediatric indication, the pediatric information is included in the applicable sections: indications and usage, dosage and administration, adverse reactions, use in specific populations, pharmacokinetics and pharmacodynamics, and clinical studies.

However, if the data are not adequate to support pediatric approval, all pediatric information on the drug appears in the section on “Use in specific populations-Pediatric Use,” which she said “will avoid the implication of approval.”

SOURCE: DR. MASUCCI/ELSEVIER GLOBAL MEDICAL NEWS

ROCKVILLE, MD. — Pediatric information in drug labels is expected to be easier to find and less confusing because of a new approach to incorporating pediatric information into the revised drug label design that is required for all new drugs approved since June last year.

At a meeting of the Food and Drug Administration's Pediatric Advisory Committee held to review pediatric adverse event reports for several drugs, Iris Masucci, Pharm.D., of the FDA's Center for Drug Evaluation and Research (CDER), provided an overview of the elements of the revised drug label.

A physician labeling rule implemented in June 2006 requires that drug labels be revised to make them more user friendly than the previous format. The label, or package insert, of any newly approved drug or biologic or supplemental efficacy approval of a drug submitted to the FDA after June 30, 2006, is required to be in the new format. Drugs approved in the 5 years before this implementation date are required to update their labeling to the new format according to a stepped timeline.

Drugs approved before that time are not required to make the change, but may do so voluntarily. The new labeling requirements also apply to biologics.

The approach on where to incorporate pediatric information into labels is a separate initiative from the new labeling format requirements. Rather, it is a more clearly defined paradigm than what has been used in the past, which will make labels more consistent in terms of how and where pediatric information is added, Dr. Masucci said in an interview.

A major change in the newly designed label is the highlights section, designed in response to feedback from physicians on what they wanted in a drug label, which appears at the beginning of the label. This is a half-page summary that provides the main information on a drug in a simple format with bullets and tables, Dr. Masucci said at the meeting.

This section includes the name of the product with the date of the initial U.S. approval; a boxed warning (if there is one); indications (which include the pharmacologic class of the drug); usage, dosage, and administration information; major changes recently made to the label; as well as dosage forms and strengths, contraindications, warning and precautions, adverse reactions, and drug interactions.

Also included is a patient counseling information statement and a section on use in specific populations, such as children.

The contents of the label include numbered sections with a specific number that corresponds to a particular section, which will be consistent for all drugs. For example, section 2 will always pertain to dosage and administration, and section 8 will always pertain to use in specific populations, which includes pediatric patients.

Other features of the new label include the consolidation of the warnings and precautions sections. Sections on drug interactions, use in specific populations, and patient counseling information—which appears in the precautions section in the old label—are now separate sections. Also, sections on clinical studies and nonclinical toxicology, previously optional, are now required, she said.

Contact information for the FDA's adverse event reporting program, MedWatch, and the drug's manufacturer for reporting adverse events are now also included in the label.

With the old format, it is difficult to determine if a drug is actually approved for pediatric use, Dr. Masucci said, noting that for example, in some tables, a pediatric dose may be listed but no pediatric data are listed.

If the new data are adequate to warrant a pediatric indication, the pediatric information is included in the applicable sections: indications and usage, dosage and administration, adverse reactions, use in specific populations, pharmacokinetics and pharmacodynamics, and clinical studies.

However, if the data are not adequate to support pediatric approval, all pediatric information on the drug appears in the section on “Use in specific populations-Pediatric Use,” which she said “will avoid the implication of approval.”

SOURCE: DR. MASUCCI/ELSEVIER GLOBAL MEDICAL NEWS

The American Cancer Society advocated routine vaccination against human papillomavirus for 11- and 12-year-old girls but cautioned that the potential impact of universal vaccination on cervical cancer rates can only be realized if those underserved populations at greatest risk have access to the vaccine, according to new guidelines released by the Society on Jan. 19.

The guidelines also recommended that girls as young as age 9 years can receive the human papillomavirus (HPV) vaccine and that females 13–18 years old should be vaccinated to catch up on missed vaccine or to complete the number of required injections.

“The vaccine holds remarkable potential, but unless the same populations of women who right now do not have access to or do not seek regular Pap tests get this vaccine, it will have limited impact,” Dr. Harmon J. Eyre, chief medical officer of the Society, said in a statement announcing the new guidelines on the use of the prophylactic HPV vaccination to prevent cervical cancer and cervical intraepithelial neoplasia (CIN).

The guidelines emphasized that whether or not a woman has been vaccinated, she should continue to be screened for CIN and for cancer. “As HPV vaccination for the prevention of cervical cancer is introduced and promoted, it remains critical that women undergo regular screening even if they have been vaccinated,” Dr. Eyre said in the statement.

The guidelines were based on a formal review of the available data on HPV vaccination conducted by an expert panel convened by the ACS and are published in CA: A Cancer Journal for Clinicians (CA Cancer J. Clin. 2007;57:7–28).

The currently available vaccine is Gardasil, approved by the Food and Drug Administration in June 2006 for females aged 9–26 years to prevent conditions caused by HPV types 6, 11, 16, and 18, the HPV types covered in the vaccine (cervical cancer, condyloma acuminatum, cervical adenocarcinoma in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, and CIN grades 1, 2, and 3). HPV types 16 and 18 cause about 70% of cervical cancers, and HPV types 6 and 11 cause about 90% of genital warts.

The guidelines concluded that there are not enough data to recommend either for or against universal vaccination of females aged 19–26 years in the general population. But deciding whether a woman in this age group should be vaccinated “should be based on an informed discussion between the woman and her health care provider regarding her risk of previous HPV exposure and potential benefit from vaccination.” Since the potential benefits are likely to lessen as a woman's number of lifetime sexual partners increases, women should “ideally” be vaccinated before potential exposure to genital HPV through sexual intercourse, the guidelines said.

The guidelines do not recommend HPV vaccination currently for women over age 26 or for men.

This year, the Society estimates that 11,150 women will be diagnosed with invasive cervical cancer in the United States, and that 3,670 women will die from cervical cancer. Most cervical cancers are caused by HPV infections, with about 70% caused by HPV types 16 and 18, which are included in Gardasil. Approximately 500,000 precancerous lesions are diagnosed annually in the United States, of which about 50%–60% can be attributed to HPV 16 and HPV 18.

A substantial, long-term impact of the vaccine on cervical cancer rates is not expected to be evident until the young girls being vaccinated reach the age of 48, the median age at which women are diagnosed with cervical cancer, the guidelines said. Ultimately, the impact on cervical cancer will be affected by factors that include coverage in at-risk populations and durability of protection. But in the short term, vaccination could potentially have a beneficial impact in terms of lower numbers of HPV infections leading to a reduced number of women with abnormal Pap smears that require a work-up and treatment, fewer abnormal Pap results, and fewer referrals for colposcopy, cervical biopsy, and genital warts (HPV 16, 11, 6, and 18 cause about 40% of histologically confirmed CIN).

The guidelines focus on Gardasil but will be updated as new vaccines become available and are approved. A second HPV vaccine, Cervarix, is not yet approved.

HPV vaccination was included for the first time in the 2007 recommended immunization schedule for children and adolescents, released earlier in January by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. The three-dose series of HPV vaccine is recommended for girls aged 11–12 but can be started at age 9; catch-up vaccination is recommended for girls and women 13–26 years old who have not been vaccinated or have not received all three injections.

The full text of the ACS guidelines is available at http://CAonline.AmCancer Soc.org

The American Cancer Society advocated routine vaccination against human papillomavirus for 11- and 12-year-old girls but cautioned that the potential impact of universal vaccination on cervical cancer rates can only be realized if those underserved populations at greatest risk have access to the vaccine, according to new guidelines released by the Society on Jan. 19.

The guidelines also recommended that girls as young as age 9 years can receive the human papillomavirus (HPV) vaccine and that females 13–18 years old should be vaccinated to catch up on missed vaccine or to complete the number of required injections.

“The vaccine holds remarkable potential, but unless the same populations of women who right now do not have access to or do not seek regular Pap tests get this vaccine, it will have limited impact,” Dr. Harmon J. Eyre, chief medical officer of the Society, said in a statement announcing the new guidelines on the use of the prophylactic HPV vaccination to prevent cervical cancer and cervical intraepithelial neoplasia (CIN).

The guidelines emphasized that whether or not a woman has been vaccinated, she should continue to be screened for CIN and for cancer. “As HPV vaccination for the prevention of cervical cancer is introduced and promoted, it remains critical that women undergo regular screening even if they have been vaccinated,” Dr. Eyre said in the statement.

The guidelines were based on a formal review of the available data on HPV vaccination conducted by an expert panel convened by the ACS and are published in CA: A Cancer Journal for Clinicians (CA Cancer J. Clin. 2007;57:7–28).

The currently available vaccine is Gardasil, approved by the Food and Drug Administration in June 2006 for females aged 9–26 years to prevent conditions caused by HPV types 6, 11, 16, and 18, the HPV types covered in the vaccine (cervical cancer, condyloma acuminatum, cervical adenocarcinoma in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, and CIN grades 1, 2, and 3). HPV types 16 and 18 cause about 70% of cervical cancers, and HPV types 6 and 11 cause about 90% of genital warts.

The guidelines concluded that there are not enough data to recommend either for or against universal vaccination of females aged 19–26 years in the general population. But deciding whether a woman in this age group should be vaccinated “should be based on an informed discussion between the woman and her health care provider regarding her risk of previous HPV exposure and potential benefit from vaccination.” Since the potential benefits are likely to lessen as a woman's number of lifetime sexual partners increases, women should “ideally” be vaccinated before potential exposure to genital HPV through sexual intercourse, the guidelines said.

The guidelines do not recommend HPV vaccination currently for women over age 26 or for men.

This year, the Society estimates that 11,150 women will be diagnosed with invasive cervical cancer in the United States, and that 3,670 women will die from cervical cancer. Most cervical cancers are caused by HPV infections, with about 70% caused by HPV types 16 and 18, which are included in Gardasil. Approximately 500,000 precancerous lesions are diagnosed annually in the United States, of which about 50%–60% can be attributed to HPV 16 and HPV 18.

A substantial, long-term impact of the vaccine on cervical cancer rates is not expected to be evident until the young girls being vaccinated reach the age of 48, the median age at which women are diagnosed with cervical cancer, the guidelines said. Ultimately, the impact on cervical cancer will be affected by factors that include coverage in at-risk populations and durability of protection. But in the short term, vaccination could potentially have a beneficial impact in terms of lower numbers of HPV infections leading to a reduced number of women with abnormal Pap smears that require a work-up and treatment, fewer abnormal Pap results, and fewer referrals for colposcopy, cervical biopsy, and genital warts (HPV 16, 11, 6, and 18 cause about 40% of histologically confirmed CIN).

The guidelines focus on Gardasil but will be updated as new vaccines become available and are approved. A second HPV vaccine, Cervarix, is not yet approved.

HPV vaccination was included for the first time in the 2007 recommended immunization schedule for children and adolescents, released earlier in January by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. The three-dose series of HPV vaccine is recommended for girls aged 11–12 but can be started at age 9; catch-up vaccination is recommended for girls and women 13–26 years old who have not been vaccinated or have not received all three injections.

The full text of the ACS guidelines is available at http://CAonline.AmCancer Soc.org

The American Cancer Society advocated routine vaccination against human papillomavirus for 11- and 12-year-old girls but cautioned that the potential impact of universal vaccination on cervical cancer rates can only be realized if those underserved populations at greatest risk have access to the vaccine, according to new guidelines released by the Society on Jan. 19.

The guidelines also recommended that girls as young as age 9 years can receive the human papillomavirus (HPV) vaccine and that females 13–18 years old should be vaccinated to catch up on missed vaccine or to complete the number of required injections.

“The vaccine holds remarkable potential, but unless the same populations of women who right now do not have access to or do not seek regular Pap tests get this vaccine, it will have limited impact,” Dr. Harmon J. Eyre, chief medical officer of the Society, said in a statement announcing the new guidelines on the use of the prophylactic HPV vaccination to prevent cervical cancer and cervical intraepithelial neoplasia (CIN).

The guidelines emphasized that whether or not a woman has been vaccinated, she should continue to be screened for CIN and for cancer. “As HPV vaccination for the prevention of cervical cancer is introduced and promoted, it remains critical that women undergo regular screening even if they have been vaccinated,” Dr. Eyre said in the statement.

The guidelines were based on a formal review of the available data on HPV vaccination conducted by an expert panel convened by the ACS and are published in CA: A Cancer Journal for Clinicians (CA Cancer J. Clin. 2007;57:7–28).

The currently available vaccine is Gardasil, approved by the Food and Drug Administration in June 2006 for females aged 9–26 years to prevent conditions caused by HPV types 6, 11, 16, and 18, the HPV types covered in the vaccine (cervical cancer, condyloma acuminatum, cervical adenocarcinoma in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, and CIN grades 1, 2, and 3). HPV types 16 and 18 cause about 70% of cervical cancers, and HPV types 6 and 11 cause about 90% of genital warts.

The guidelines concluded that there are not enough data to recommend either for or against universal vaccination of females aged 19–26 years in the general population. But deciding whether a woman in this age group should be vaccinated “should be based on an informed discussion between the woman and her health care provider regarding her risk of previous HPV exposure and potential benefit from vaccination.” Since the potential benefits are likely to lessen as a woman's number of lifetime sexual partners increases, women should “ideally” be vaccinated before potential exposure to genital HPV through sexual intercourse, the guidelines said.

The guidelines do not recommend HPV vaccination currently for women over age 26 or for men.

This year, the Society estimates that 11,150 women will be diagnosed with invasive cervical cancer in the United States, and that 3,670 women will die from cervical cancer. Most cervical cancers are caused by HPV infections, with about 70% caused by HPV types 16 and 18, which are included in Gardasil. Approximately 500,000 precancerous lesions are diagnosed annually in the United States, of which about 50%–60% can be attributed to HPV 16 and HPV 18.

A substantial, long-term impact of the vaccine on cervical cancer rates is not expected to be evident until the young girls being vaccinated reach the age of 48, the median age at which women are diagnosed with cervical cancer, the guidelines said. Ultimately, the impact on cervical cancer will be affected by factors that include coverage in at-risk populations and durability of protection. But in the short term, vaccination could potentially have a beneficial impact in terms of lower numbers of HPV infections leading to a reduced number of women with abnormal Pap smears that require a work-up and treatment, fewer abnormal Pap results, and fewer referrals for colposcopy, cervical biopsy, and genital warts (HPV 16, 11, 6, and 18 cause about 40% of histologically confirmed CIN).

The guidelines focus on Gardasil but will be updated as new vaccines become available and are approved. A second HPV vaccine, Cervarix, is not yet approved.

HPV vaccination was included for the first time in the 2007 recommended immunization schedule for children and adolescents, released earlier in January by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American Academy of Family Physicians. The three-dose series of HPV vaccine is recommended for girls aged 11–12 but can be started at age 9; catch-up vaccination is recommended for girls and women 13–26 years old who have not been vaccinated or have not received all three injections.

The full text of the ACS guidelines is available at http://CAonline.AmCancer Soc.org