Elizabeth Mechcatie

Strong evidence shows that prompt treatment of patients who are successfully resuscitated after cardiac arrest can improve outcomes, including mortality, according to a consensus statement on post-cardiac arrest syndrome.

Post-cardiac arrest syndrome, a new term proposed by the authors of the statement, “is a unique and complex combination of pathophysiological processes,” they said. The components are brain injury; myocardial dysfunction; the systemic ischemia/reperfusion response (including intravascular volume depletion, impaired oxygen delivery and utilization, and increased susceptibility to infection); and the underlying disease that caused the arrest (such as acute coronary syndrome [ACS] or pulmonary disease), which contribute to the high mortality rate among patients who are resuscitated, according to the statement. But this syndrome “will not occur” if resumption of spontaneous circulation (ROSC) is rapidly achieved after a cardiac arrest, they said.

They also point out that an increasing body of evidence suggests that the components of post-cardiac arrest syndrome are “potentially treatable” and “provides the essential proof of concept that interventions initiated after ROSC can improve outcome.”

The statement, which focuses on the epidemiology, pathophysiology, and prognostication of post-cardiac arrest syndrome, is intended to “provide a resource for organization of post-cardiac arrest care,” and to identify areas of research that could potentially improve outcomes of patients who are successfully resuscitated after a cardiac arrest. It was issued by the International Liaison Committee on Resuscitation and other medical organizations, and published online in Circulation (doi:10.1161/CIRCULATIONAHA.108.190652).

“Resuscitation of the cardiac arrest patient does not end when the patient regains a pulse,” at which point, the patient has only has a 30% chance of surviving to hospital discharge, Dr. Robert W. Neumar, head of the statement writing committee, said in an interview.

Interventions initiated after a pulse is restarted will improve outcomes, and include therapeutic hypothermia and percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), which is common in patients with out-of-hospital cardiac arrest, noted Dr. Neumar, associate professor of emergency medicine and associate director of the Center for Resuscitation Science at the University of Pennsylvania, Philadelphia.

The statement points out that the overall prognosis after ROSC has not improved since the first large report on patients treated for cardiac arrest was published in 1953, reporting an in-hospital mortality rate of 50%. The authors cite the National Registry of CardioPulmonary Resuscitation, published in 2006, which found that in-hospital mortality was 67% among nearly 20,000 adults and 55% among 524 children who regained spontaneous circulation after a cardiac arrest. These rates also vary by region and institution, and despite advances that have improved ROSC rates, they have not translated into improvements in hospital discharge rates and long-term survival.

Recommendations for treatment strategies include using mild therapeutic hypothermia (cooling down to 32° C to 34° C, or 86.9° F to 93.2° F for at least 12–24 hours), started as soon as possible for unconscious adults with who are successfully resuscitated outside of the hospital after a cardiac arrest. Preclinical and clinical data “strongly” support the use of this modality as an effective treatment for post-cardiac arrest syndrome, the authors wrote.

They also recommend immediate coronary angiography for patients with electrocardiographic evidence of STEMI, “with subsequent PCI if indicated,” or thrombolytic therapy if PCI is not available. In consideration of how common ACS is among patients who have a cardiac arrest outside of the hospital, it is “appropriate” to consider angiography whenever ACS is suspected in post-cardiac arrest patients, they added.

Other recommendations include prompt treatment of prolonged seizures, frequent monitoring of blood glucose, treatment of hyperglycemia, and avoidance of unnecessary arterial hyperoxia.

The statement includes a section on post-cardiac arrest prognostication. “We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients,” Dr. Neumar said in the interview. “With the advent of neuroprotective interventions such as therapeutic hypothermia, currently used prognostication strategies may not be reliable.”

The statement was from the International Liaison Committee on Resuscitation (the American Heart Association, Australian Resuscitation Council, the Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, Resuscitation Council of South Africa, and the New Zealand Resuscitation Council) and the AHA Emergency Cardiovascular Care Committee; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiopulmonary, Perioperative, and Critical Care; Council on Clinical Cardiology; and the Stroke Council. It was endorsed by the American College of Emergency Physicians, Society for Academic Emergency Medicine, and Society of Critical Care Medicine.

'We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients.' DR. NEUMAR

Strong evidence shows that prompt treatment of patients who are successfully resuscitated after cardiac arrest can improve outcomes, including mortality, according to a consensus statement on post-cardiac arrest syndrome.

Post-cardiac arrest syndrome, a new term proposed by the authors of the statement, “is a unique and complex combination of pathophysiological processes,” they said. The components are brain injury; myocardial dysfunction; the systemic ischemia/reperfusion response (including intravascular volume depletion, impaired oxygen delivery and utilization, and increased susceptibility to infection); and the underlying disease that caused the arrest (such as acute coronary syndrome [ACS] or pulmonary disease), which contribute to the high mortality rate among patients who are resuscitated, according to the statement. But this syndrome “will not occur” if resumption of spontaneous circulation (ROSC) is rapidly achieved after a cardiac arrest, they said.

They also point out that an increasing body of evidence suggests that the components of post-cardiac arrest syndrome are “potentially treatable” and “provides the essential proof of concept that interventions initiated after ROSC can improve outcome.”

The statement, which focuses on the epidemiology, pathophysiology, and prognostication of post-cardiac arrest syndrome, is intended to “provide a resource for organization of post-cardiac arrest care,” and to identify areas of research that could potentially improve outcomes of patients who are successfully resuscitated after a cardiac arrest. It was issued by the International Liaison Committee on Resuscitation and other medical organizations, and published online in Circulation (doi:10.1161/CIRCULATIONAHA.108.190652).

“Resuscitation of the cardiac arrest patient does not end when the patient regains a pulse,” at which point, the patient has only has a 30% chance of surviving to hospital discharge, Dr. Robert W. Neumar, head of the statement writing committee, said in an interview.

Interventions initiated after a pulse is restarted will improve outcomes, and include therapeutic hypothermia and percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), which is common in patients with out-of-hospital cardiac arrest, noted Dr. Neumar, associate professor of emergency medicine and associate director of the Center for Resuscitation Science at the University of Pennsylvania, Philadelphia.

The statement points out that the overall prognosis after ROSC has not improved since the first large report on patients treated for cardiac arrest was published in 1953, reporting an in-hospital mortality rate of 50%. The authors cite the National Registry of CardioPulmonary Resuscitation, published in 2006, which found that in-hospital mortality was 67% among nearly 20,000 adults and 55% among 524 children who regained spontaneous circulation after a cardiac arrest. These rates also vary by region and institution, and despite advances that have improved ROSC rates, they have not translated into improvements in hospital discharge rates and long-term survival.

Recommendations for treatment strategies include using mild therapeutic hypothermia (cooling down to 32° C to 34° C, or 86.9° F to 93.2° F for at least 12–24 hours), started as soon as possible for unconscious adults with who are successfully resuscitated outside of the hospital after a cardiac arrest. Preclinical and clinical data “strongly” support the use of this modality as an effective treatment for post-cardiac arrest syndrome, the authors wrote.

They also recommend immediate coronary angiography for patients with electrocardiographic evidence of STEMI, “with subsequent PCI if indicated,” or thrombolytic therapy if PCI is not available. In consideration of how common ACS is among patients who have a cardiac arrest outside of the hospital, it is “appropriate” to consider angiography whenever ACS is suspected in post-cardiac arrest patients, they added.

Other recommendations include prompt treatment of prolonged seizures, frequent monitoring of blood glucose, treatment of hyperglycemia, and avoidance of unnecessary arterial hyperoxia.

The statement includes a section on post-cardiac arrest prognostication. “We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients,” Dr. Neumar said in the interview. “With the advent of neuroprotective interventions such as therapeutic hypothermia, currently used prognostication strategies may not be reliable.”

The statement was from the International Liaison Committee on Resuscitation (the American Heart Association, Australian Resuscitation Council, the Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, Resuscitation Council of South Africa, and the New Zealand Resuscitation Council) and the AHA Emergency Cardiovascular Care Committee; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiopulmonary, Perioperative, and Critical Care; Council on Clinical Cardiology; and the Stroke Council. It was endorsed by the American College of Emergency Physicians, Society for Academic Emergency Medicine, and Society of Critical Care Medicine.

'We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients.' DR. NEUMAR

Strong evidence shows that prompt treatment of patients who are successfully resuscitated after cardiac arrest can improve outcomes, including mortality, according to a consensus statement on post-cardiac arrest syndrome.

Post-cardiac arrest syndrome, a new term proposed by the authors of the statement, “is a unique and complex combination of pathophysiological processes,” they said. The components are brain injury; myocardial dysfunction; the systemic ischemia/reperfusion response (including intravascular volume depletion, impaired oxygen delivery and utilization, and increased susceptibility to infection); and the underlying disease that caused the arrest (such as acute coronary syndrome [ACS] or pulmonary disease), which contribute to the high mortality rate among patients who are resuscitated, according to the statement. But this syndrome “will not occur” if resumption of spontaneous circulation (ROSC) is rapidly achieved after a cardiac arrest, they said.

They also point out that an increasing body of evidence suggests that the components of post-cardiac arrest syndrome are “potentially treatable” and “provides the essential proof of concept that interventions initiated after ROSC can improve outcome.”

The statement, which focuses on the epidemiology, pathophysiology, and prognostication of post-cardiac arrest syndrome, is intended to “provide a resource for organization of post-cardiac arrest care,” and to identify areas of research that could potentially improve outcomes of patients who are successfully resuscitated after a cardiac arrest. It was issued by the International Liaison Committee on Resuscitation and other medical organizations, and published online in Circulation (doi:10.1161/CIRCULATIONAHA.108.190652).

“Resuscitation of the cardiac arrest patient does not end when the patient regains a pulse,” at which point, the patient has only has a 30% chance of surviving to hospital discharge, Dr. Robert W. Neumar, head of the statement writing committee, said in an interview.

Interventions initiated after a pulse is restarted will improve outcomes, and include therapeutic hypothermia and percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), which is common in patients with out-of-hospital cardiac arrest, noted Dr. Neumar, associate professor of emergency medicine and associate director of the Center for Resuscitation Science at the University of Pennsylvania, Philadelphia.

The statement points out that the overall prognosis after ROSC has not improved since the first large report on patients treated for cardiac arrest was published in 1953, reporting an in-hospital mortality rate of 50%. The authors cite the National Registry of CardioPulmonary Resuscitation, published in 2006, which found that in-hospital mortality was 67% among nearly 20,000 adults and 55% among 524 children who regained spontaneous circulation after a cardiac arrest. These rates also vary by region and institution, and despite advances that have improved ROSC rates, they have not translated into improvements in hospital discharge rates and long-term survival.

Recommendations for treatment strategies include using mild therapeutic hypothermia (cooling down to 32° C to 34° C, or 86.9° F to 93.2° F for at least 12–24 hours), started as soon as possible for unconscious adults with who are successfully resuscitated outside of the hospital after a cardiac arrest. Preclinical and clinical data “strongly” support the use of this modality as an effective treatment for post-cardiac arrest syndrome, the authors wrote.

They also recommend immediate coronary angiography for patients with electrocardiographic evidence of STEMI, “with subsequent PCI if indicated,” or thrombolytic therapy if PCI is not available. In consideration of how common ACS is among patients who have a cardiac arrest outside of the hospital, it is “appropriate” to consider angiography whenever ACS is suspected in post-cardiac arrest patients, they added.

Other recommendations include prompt treatment of prolonged seizures, frequent monitoring of blood glucose, treatment of hyperglycemia, and avoidance of unnecessary arterial hyperoxia.

The statement includes a section on post-cardiac arrest prognostication. “We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients,” Dr. Neumar said in the interview. “With the advent of neuroprotective interventions such as therapeutic hypothermia, currently used prognostication strategies may not be reliable.”

The statement was from the International Liaison Committee on Resuscitation (the American Heart Association, Australian Resuscitation Council, the Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, Resuscitation Council of South Africa, and the New Zealand Resuscitation Council) and the AHA Emergency Cardiovascular Care Committee; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiopulmonary, Perioperative, and Critical Care; Council on Clinical Cardiology; and the Stroke Council. It was endorsed by the American College of Emergency Physicians, Society for Academic Emergency Medicine, and Society of Critical Care Medicine.

'We need to reevaluate how we prognosticate poor outcomes in post-cardiac arrest patients.' DR. NEUMAR

From 2001 through 2006, the number of HIV/AIDS diagnoses among men who have sex with men increased by nearly 9% in 33 states, with particularly high increases among black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses among men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM, and 4% were among MSM who also injected illicit drugs. Diagnoses during the same time period dropped in all transmission categories except for MSM (MMWR 2007;57: 681-6).

Of the cases diagnosed among MSM, 64% were in men aged 25-44 years. There was a 12% increase in diagnoses among all black MSM. Diagnoses among black MSM aged 13-24 years increased by 93%, a rate that was about twofold greater than the rate of increase among white MSM in the same age group.

Asian/Pacific Islanders aged 13-24 years saw the largest proportionate increase in HIV/AIDS diagnoses.

In that group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

"These findings underscore the need for continued effective testing and risk reduction interventions for MSM," particularly for those individuals younger than age 25, according to the CDC report.

As an example, the report cites an intervention targeted to young black MSM in North Carolina (one of the 33 states), implemented by the CDC, in collaboration the state health department and local organizations that successfully reduced their high-risk sexual behavior and the number of sex partners with whom they engaged in high-risk sexual behaviors.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all of the states.

From 2001 through 2006, the number of HIV/AIDS diagnoses among men who have sex with men increased by nearly 9% in 33 states, with particularly high increases among black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses among men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM, and 4% were among MSM who also injected illicit drugs. Diagnoses during the same time period dropped in all transmission categories except for MSM (MMWR 2007;57: 681-6).

Of the cases diagnosed among MSM, 64% were in men aged 25-44 years. There was a 12% increase in diagnoses among all black MSM. Diagnoses among black MSM aged 13-24 years increased by 93%, a rate that was about twofold greater than the rate of increase among white MSM in the same age group.

Asian/Pacific Islanders aged 13-24 years saw the largest proportionate increase in HIV/AIDS diagnoses.

In that group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

"These findings underscore the need for continued effective testing and risk reduction interventions for MSM," particularly for those individuals younger than age 25, according to the CDC report.

As an example, the report cites an intervention targeted to young black MSM in North Carolina (one of the 33 states), implemented by the CDC, in collaboration the state health department and local organizations that successfully reduced their high-risk sexual behavior and the number of sex partners with whom they engaged in high-risk sexual behaviors.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all of the states.

From 2001 through 2006, the number of HIV/AIDS diagnoses among men who have sex with men increased by nearly 9% in 33 states, with particularly high increases among black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses among men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM, and 4% were among MSM who also injected illicit drugs. Diagnoses during the same time period dropped in all transmission categories except for MSM (MMWR 2007;57: 681-6).

Of the cases diagnosed among MSM, 64% were in men aged 25-44 years. There was a 12% increase in diagnoses among all black MSM. Diagnoses among black MSM aged 13-24 years increased by 93%, a rate that was about twofold greater than the rate of increase among white MSM in the same age group.

Asian/Pacific Islanders aged 13-24 years saw the largest proportionate increase in HIV/AIDS diagnoses.

In that group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

"These findings underscore the need for continued effective testing and risk reduction interventions for MSM," particularly for those individuals younger than age 25, according to the CDC report.

As an example, the report cites an intervention targeted to young black MSM in North Carolina (one of the 33 states), implemented by the CDC, in collaboration the state health department and local organizations that successfully reduced their high-risk sexual behavior and the number of sex partners with whom they engaged in high-risk sexual behaviors.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all of the states.

SILVER SPRING, MD. — An expert panel has unanimously recommended that ustekinumab, a novel human monoclonal antibody, be approved for treating adults with moderate to severe plaque psoriasis, but said more safety data were necessary about potential long-term risks associated with treatment, particularly malignancies.

At a meeting of the Food and Drug Administration's dermatologic and ophthalmic drugs advisory panel in June, the panel voted 11 to 0 to support approval of ustekinumab, which is made by Centocor Inc.

It also unanimously agreed that more safety data in more patients treated for a longer period of time was critical, and that the potential for malignancy linked to ustekinumab was based on the theoretical risk as well as some animal data indicating an increased carcinogenic risk within the cytokines interleukin-12 (IL-12) and interleu- kin-23 (IL-23), which ustekinumab targets.

Ustekinumab is a first in class new entity that has not been approved for any other indication. The company has proposed that the first two doses of ustekinumab be administered 4 weeks apart, then every 12 weeks during maintenance treatment; it is administered by subcutaneous injection.

Two phase III studies compared two doses of ustekinumab with placebo in almost 2,000 adult patients who had had plaque psoriasis for at least 6 months, with baseline Psoriasis Area Severity Index (PASI) scores of 12 or higher. At 12 weeks, the proportion of patients with a PASI 75 response (at least a 75% improvement in PASI score), the primary efficacy end point, and the proportion who had a physician's global assessment (PGA) of cleared or minimal plaques, a secondary end point, were significantly greater in those on ustemnimab than in those on placebo, according to the FDA.

In one study, 67% of those on the 45-mg dose and 66% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 3% of those on placebo. In the second study, 67% of those on the 45-mg dose and 76% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 4% of those on placebo. In the studies, the proportion of patients who achieved a PGA of cleared or minimal plaques at 12 weeks ranged from 60% to 73% of those on ustekinumab, compared with 4%–5% in those on placebo.

Because of its mechanism of action, treatment may increase the risk for malignancies, and other adverse events, such as serious infections. In the studies, rates of serious infections and malignancies were low “and consistent with the expected background rates,” said Centocor.

The FDA usually follows its advisory panels' recomendations, which are not binding. Other biologic therapies approved for psoriasis are alefacept (Amevive), efalizumab (Raptiva), infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira).

SILVER SPRING, MD. — An expert panel has unanimously recommended that ustekinumab, a novel human monoclonal antibody, be approved for treating adults with moderate to severe plaque psoriasis, but said more safety data were necessary about potential long-term risks associated with treatment, particularly malignancies.

At a meeting of the Food and Drug Administration's dermatologic and ophthalmic drugs advisory panel in June, the panel voted 11 to 0 to support approval of ustekinumab, which is made by Centocor Inc.

It also unanimously agreed that more safety data in more patients treated for a longer period of time was critical, and that the potential for malignancy linked to ustekinumab was based on the theoretical risk as well as some animal data indicating an increased carcinogenic risk within the cytokines interleukin-12 (IL-12) and interleu- kin-23 (IL-23), which ustekinumab targets.

Ustekinumab is a first in class new entity that has not been approved for any other indication. The company has proposed that the first two doses of ustekinumab be administered 4 weeks apart, then every 12 weeks during maintenance treatment; it is administered by subcutaneous injection.

Two phase III studies compared two doses of ustekinumab with placebo in almost 2,000 adult patients who had had plaque psoriasis for at least 6 months, with baseline Psoriasis Area Severity Index (PASI) scores of 12 or higher. At 12 weeks, the proportion of patients with a PASI 75 response (at least a 75% improvement in PASI score), the primary efficacy end point, and the proportion who had a physician's global assessment (PGA) of cleared or minimal plaques, a secondary end point, were significantly greater in those on ustemnimab than in those on placebo, according to the FDA.

In one study, 67% of those on the 45-mg dose and 66% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 3% of those on placebo. In the second study, 67% of those on the 45-mg dose and 76% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 4% of those on placebo. In the studies, the proportion of patients who achieved a PGA of cleared or minimal plaques at 12 weeks ranged from 60% to 73% of those on ustekinumab, compared with 4%–5% in those on placebo.

Because of its mechanism of action, treatment may increase the risk for malignancies, and other adverse events, such as serious infections. In the studies, rates of serious infections and malignancies were low “and consistent with the expected background rates,” said Centocor.

The FDA usually follows its advisory panels' recomendations, which are not binding. Other biologic therapies approved for psoriasis are alefacept (Amevive), efalizumab (Raptiva), infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira).

SILVER SPRING, MD. — An expert panel has unanimously recommended that ustekinumab, a novel human monoclonal antibody, be approved for treating adults with moderate to severe plaque psoriasis, but said more safety data were necessary about potential long-term risks associated with treatment, particularly malignancies.

At a meeting of the Food and Drug Administration's dermatologic and ophthalmic drugs advisory panel in June, the panel voted 11 to 0 to support approval of ustekinumab, which is made by Centocor Inc.

It also unanimously agreed that more safety data in more patients treated for a longer period of time was critical, and that the potential for malignancy linked to ustekinumab was based on the theoretical risk as well as some animal data indicating an increased carcinogenic risk within the cytokines interleukin-12 (IL-12) and interleu- kin-23 (IL-23), which ustekinumab targets.

Ustekinumab is a first in class new entity that has not been approved for any other indication. The company has proposed that the first two doses of ustekinumab be administered 4 weeks apart, then every 12 weeks during maintenance treatment; it is administered by subcutaneous injection.

Two phase III studies compared two doses of ustekinumab with placebo in almost 2,000 adult patients who had had plaque psoriasis for at least 6 months, with baseline Psoriasis Area Severity Index (PASI) scores of 12 or higher. At 12 weeks, the proportion of patients with a PASI 75 response (at least a 75% improvement in PASI score), the primary efficacy end point, and the proportion who had a physician's global assessment (PGA) of cleared or minimal plaques, a secondary end point, were significantly greater in those on ustemnimab than in those on placebo, according to the FDA.

In one study, 67% of those on the 45-mg dose and 66% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 3% of those on placebo. In the second study, 67% of those on the 45-mg dose and 76% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 4% of those on placebo. In the studies, the proportion of patients who achieved a PGA of cleared or minimal plaques at 12 weeks ranged from 60% to 73% of those on ustekinumab, compared with 4%–5% in those on placebo.

Because of its mechanism of action, treatment may increase the risk for malignancies, and other adverse events, such as serious infections. In the studies, rates of serious infections and malignancies were low “and consistent with the expected background rates,” said Centocor.

The FDA usually follows its advisory panels' recomendations, which are not binding. Other biologic therapies approved for psoriasis are alefacept (Amevive), efalizumab (Raptiva), infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira).

From 2001 through 2006, the number of HIV/AIDS diagnoses in men who have sex with men increased by nearly 9% in 33 states, with particularly high increases in black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses in men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM and 4% were among MSM who also injected illicit drugs. Diagnoses during this time period dropped in all transmission categories except for MSM (MMWR 2007;57:681-6).

Of the cases diagnosed among MSM, 64% were in men who were aged 25–44 years. There was a 12% increase in diagnoses in all black MSM. Diagnoses in black MSM aged 13–24 years increased by 93%, a rate that was about twofold greater than the rate of increase in white MSM in the same age group.

Asian/Pacific Islanders aged 13–24 years saw the largest proportionate increase in HIV/AIDS diagnoses. In this group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

“These findings underscore the need for continued effective testing and risk reduction interventions for MSM,” particularly for those younger than age 25 years, according to the report.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all the states.

From 2001 through 2006, the number of HIV/AIDS diagnoses in men who have sex with men increased by nearly 9% in 33 states, with particularly high increases in black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses in men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM and 4% were among MSM who also injected illicit drugs. Diagnoses during this time period dropped in all transmission categories except for MSM (MMWR 2007;57:681-6).

Of the cases diagnosed among MSM, 64% were in men who were aged 25–44 years. There was a 12% increase in diagnoses in all black MSM. Diagnoses in black MSM aged 13–24 years increased by 93%, a rate that was about twofold greater than the rate of increase in white MSM in the same age group.

Asian/Pacific Islanders aged 13–24 years saw the largest proportionate increase in HIV/AIDS diagnoses. In this group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

“These findings underscore the need for continued effective testing and risk reduction interventions for MSM,” particularly for those younger than age 25 years, according to the report.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all the states.

From 2001 through 2006, the number of HIV/AIDS diagnoses in men who have sex with men increased by nearly 9% in 33 states, with particularly high increases in black men and Asian/Pacific Islanders under age 25 years, according to the Centers for Disease Control and Prevention.

The CDC analysis of trends in HIV/AIDS diagnoses in men who have sex with men (MSM) estimated that 214,379 people were diagnosed with HIV/AIDS, of which 46% were among MSM and 4% were among MSM who also injected illicit drugs. Diagnoses during this time period dropped in all transmission categories except for MSM (MMWR 2007;57:681-6).

Of the cases diagnosed among MSM, 64% were in men who were aged 25–44 years. There was a 12% increase in diagnoses in all black MSM. Diagnoses in black MSM aged 13–24 years increased by 93%, a rate that was about twofold greater than the rate of increase in white MSM in the same age group.

Asian/Pacific Islanders aged 13–24 years saw the largest proportionate increase in HIV/AIDS diagnoses. In this group, HIV/AIDS diagnoses increased by 256% (an estimated annual increase of almost 31%). Among MSM in this younger age group, the annual percentage increases in diagnoses were statistically significant in all racial/ethnic populations, with the exception of American Indian and Alaska Natives.

“These findings underscore the need for continued effective testing and risk reduction interventions for MSM,” particularly for those younger than age 25 years, according to the report.

Among the limitations of the report, the 33 states are not representative of all HIV-positive people in the United States. However, the racial and ethnic disparities observed are similar to those observed for AIDS cases in all the states.

The system that uses letters of the alphabet to categorize drugs' pregnancy and lactation risks will be eliminated and replaced by a more consistent format designed to be more comprehensive and useful to health care professionals and patients who are of childbearing age, pregnant, or breast-feeding, the Food and Drug Administration recently announced.

The proposed rule would change the content and format of the pregnancy and lactation information that is included in the labeling of human drugs and biologics. Under the proposal, the drug label “would explain the potential benefits and risks for the mother, and the developing baby or fetus, and how these risks may change over the course of pregnancy,” Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs, said during a media briefing.

Established in 1979, the current category system uses the letters A, B, C, D, and X to indicate degrees of risk associated with a drug or biologic during pregnancy. The system has been criticized by many in the medical community as providing an inaccurate and oversimplified view of the information available on a drug, and has caused difficulty in updating specific labels as new information on drugs becomes available.

Under the proposed rule, labels would also include “relevant clinical information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and/or lactation,” according to the FDA.

The letter system would be replaced by a pregnancy section, which would contain three subsections:

▸ The “Fetal Risk Summary” would summarize known risks of the drug for a fetus and, in the event of a risk, would explain whether that risk is based on human and/or animal data.

▸ “Clinical Considerations” would include information about the effects of a drug taken by a woman before she knows she is pregnant.

▸ “Data” would provide details on the available human and animal data found in the fetal risk summary on the effects of the drug.

The pregnancy section would also contain information about available pregnancy registries of women exposed to specific drugs.

There would also be a lactation section, which would include the same three subsections used in the pregnancy section.

The section on labor and delivery, which is included in current labels, would be eliminated; information on a drug used during labor and delivery would be included in the pregnancy section.

Once the rule is finalized, the new format would be required for the labels of newly approved drugs. Manufacturers of drugs that are already approved would be required to comply over a certain number of years or when another change is made to the label.

The system that uses letters of the alphabet to categorize drugs' pregnancy and lactation risks will be eliminated and replaced by a more consistent format designed to be more comprehensive and useful to health care professionals and patients who are of childbearing age, pregnant, or breast-feeding, the Food and Drug Administration recently announced.

The proposed rule would change the content and format of the pregnancy and lactation information that is included in the labeling of human drugs and biologics. Under the proposal, the drug label “would explain the potential benefits and risks for the mother, and the developing baby or fetus, and how these risks may change over the course of pregnancy,” Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs, said during a media briefing.

Established in 1979, the current category system uses the letters A, B, C, D, and X to indicate degrees of risk associated with a drug or biologic during pregnancy. The system has been criticized by many in the medical community as providing an inaccurate and oversimplified view of the information available on a drug, and has caused difficulty in updating specific labels as new information on drugs becomes available.

Under the proposed rule, labels would also include “relevant clinical information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and/or lactation,” according to the FDA.

The letter system would be replaced by a pregnancy section, which would contain three subsections:

▸ The “Fetal Risk Summary” would summarize known risks of the drug for a fetus and, in the event of a risk, would explain whether that risk is based on human and/or animal data.

▸ “Clinical Considerations” would include information about the effects of a drug taken by a woman before she knows she is pregnant.

▸ “Data” would provide details on the available human and animal data found in the fetal risk summary on the effects of the drug.

The pregnancy section would also contain information about available pregnancy registries of women exposed to specific drugs.

There would also be a lactation section, which would include the same three subsections used in the pregnancy section.

The section on labor and delivery, which is included in current labels, would be eliminated; information on a drug used during labor and delivery would be included in the pregnancy section.

Once the rule is finalized, the new format would be required for the labels of newly approved drugs. Manufacturers of drugs that are already approved would be required to comply over a certain number of years or when another change is made to the label.

The system that uses letters of the alphabet to categorize drugs' pregnancy and lactation risks will be eliminated and replaced by a more consistent format designed to be more comprehensive and useful to health care professionals and patients who are of childbearing age, pregnant, or breast-feeding, the Food and Drug Administration recently announced.

The proposed rule would change the content and format of the pregnancy and lactation information that is included in the labeling of human drugs and biologics. Under the proposal, the drug label “would explain the potential benefits and risks for the mother, and the developing baby or fetus, and how these risks may change over the course of pregnancy,” Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs, said during a media briefing.

Established in 1979, the current category system uses the letters A, B, C, D, and X to indicate degrees of risk associated with a drug or biologic during pregnancy. The system has been criticized by many in the medical community as providing an inaccurate and oversimplified view of the information available on a drug, and has caused difficulty in updating specific labels as new information on drugs becomes available.

Under the proposed rule, labels would also include “relevant clinical information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and/or lactation,” according to the FDA.

The letter system would be replaced by a pregnancy section, which would contain three subsections:

▸ The “Fetal Risk Summary” would summarize known risks of the drug for a fetus and, in the event of a risk, would explain whether that risk is based on human and/or animal data.

▸ “Clinical Considerations” would include information about the effects of a drug taken by a woman before she knows she is pregnant.

▸ “Data” would provide details on the available human and animal data found in the fetal risk summary on the effects of the drug.

The pregnancy section would also contain information about available pregnancy registries of women exposed to specific drugs.

There would also be a lactation section, which would include the same three subsections used in the pregnancy section.

The section on labor and delivery, which is included in current labels, would be eliminated; information on a drug used during labor and delivery would be included in the pregnancy section.

Once the rule is finalized, the new format would be required for the labels of newly approved drugs. Manufacturers of drugs that are already approved would be required to comply over a certain number of years or when another change is made to the label.

Information about the increased risk of cancer-related deaths in patients who have used three or more tubes of becaplermin is now included in a boxed warning on the label of the diabetic foot and leg ulcer treatment.

On June 6, the Food and Drug Administration announced that the warning had been added to the label of becaplermin (Regranex), a recombinant human platelet-derived growth factor that was approved in 1997. It is marketed as Regranex Gel 0.01% for treating nonhealing diabetic leg and foot ulcers.

The boxed warning says that the increased risk of mortality was observed in a postmarketing retrospective cohort study in patients who had been treated with three or more tubes, and advises that Regranex gel should only be used “when the benefits can be expected to outweigh the risks.” The warning also says that it should be used “with caution” in patients with a known malignancy.

The retrospective study compared cancer incidence and cancer mortality among 1,622 patients who had been treated with Regranex to 2,809 similar patients who had not been treated with Regranex. The study found that the incidence of cancer was not increased among those in the Regranex group, but the risk of cancer mortality was five times higher among those patients who had been exposed to three or more tubes of Regranex.

“No single type of cancer was identified, but rather deaths from all types of cancer combined were observed,” according to the FDA's statement announcing the change in the label.

In March, the FDA announced that it was conducting a safety review of Regranex after receiving information about the epidemiologic study, and that labeling changes were possible. The changes in the label also are explained in a “Dear Healthcare Professional” letter issued by the manufacturer, Ortho-McNeil.

Because it is a growth factor and promotes cellular proliferation and angiogenesis, the manufacturer of Regranex has monitored patients treated with the product for an increased risk of cancer or other adverse effects in postapproval safety studies.

A long-term safety study which was completed in 2001 found that cancer-related deaths were higher among patients who had used Regranex than among those patients who had not used it, according to the FDA statement. This was followed by the retrospective study, which compared cancer rates and overall cancer mortality among patients with similar diagnoses and drug use in a medical claims database.

The rate of deaths from all cancers among the patients who had been treated with three or more tubes of Regranex was 3.9 per 1,000 person-years, compared with 0.9 per 1,000 person-years among the comparators, an adjusted rate ratio of 5.2, according to the Ortho-McNeil letter. (The rate ratio was adjusted for several possible confounders.)

The letter points out that the results “were consistent with no overall increase in cancer incidence” among the patients who had been exposed to the Regranex diabetic ulcer treatment: The rate of all cancers was 10.2 per 1,000 person-years among those patients who were treated with Regranex, compared with 9.1 per 1,000 person-years among the comparators for a 1.2 adjusted rate ratio. The “types of cancers were varied and were remote from the site of treatment,” the company said in its letter.

A Web link to the FDA's update and a link to the manufacturer's letter can be accessed at www.fda.gov/cder/drug/infopage/becaplermin/default.htm

Any serious or unexpected adverse events believed to be associated with Regranex can be reported to the manufacturer at 888-734-7263 or online with the Food and Drug Administration MedWatch program at www.fda.gov/medwatch/report.htm.

Information about the increased risk of cancer-related deaths in patients who have used three or more tubes of becaplermin is now included in a boxed warning on the label of the diabetic foot and leg ulcer treatment.

On June 6, the Food and Drug Administration announced that the warning had been added to the label of becaplermin (Regranex), a recombinant human platelet-derived growth factor that was approved in 1997. It is marketed as Regranex Gel 0.01% for treating nonhealing diabetic leg and foot ulcers.

The boxed warning says that the increased risk of mortality was observed in a postmarketing retrospective cohort study in patients who had been treated with three or more tubes, and advises that Regranex gel should only be used “when the benefits can be expected to outweigh the risks.” The warning also says that it should be used “with caution” in patients with a known malignancy.

The retrospective study compared cancer incidence and cancer mortality among 1,622 patients who had been treated with Regranex to 2,809 similar patients who had not been treated with Regranex. The study found that the incidence of cancer was not increased among those in the Regranex group, but the risk of cancer mortality was five times higher among those patients who had been exposed to three or more tubes of Regranex.

“No single type of cancer was identified, but rather deaths from all types of cancer combined were observed,” according to the FDA's statement announcing the change in the label.

In March, the FDA announced that it was conducting a safety review of Regranex after receiving information about the epidemiologic study, and that labeling changes were possible. The changes in the label also are explained in a “Dear Healthcare Professional” letter issued by the manufacturer, Ortho-McNeil.

Because it is a growth factor and promotes cellular proliferation and angiogenesis, the manufacturer of Regranex has monitored patients treated with the product for an increased risk of cancer or other adverse effects in postapproval safety studies.

A long-term safety study which was completed in 2001 found that cancer-related deaths were higher among patients who had used Regranex than among those patients who had not used it, according to the FDA statement. This was followed by the retrospective study, which compared cancer rates and overall cancer mortality among patients with similar diagnoses and drug use in a medical claims database.

The rate of deaths from all cancers among the patients who had been treated with three or more tubes of Regranex was 3.9 per 1,000 person-years, compared with 0.9 per 1,000 person-years among the comparators, an adjusted rate ratio of 5.2, according to the Ortho-McNeil letter. (The rate ratio was adjusted for several possible confounders.)

The letter points out that the results “were consistent with no overall increase in cancer incidence” among the patients who had been exposed to the Regranex diabetic ulcer treatment: The rate of all cancers was 10.2 per 1,000 person-years among those patients who were treated with Regranex, compared with 9.1 per 1,000 person-years among the comparators for a 1.2 adjusted rate ratio. The “types of cancers were varied and were remote from the site of treatment,” the company said in its letter.

A Web link to the FDA's update and a link to the manufacturer's letter can be accessed at www.fda.gov/cder/drug/infopage/becaplermin/default.htm

Any serious or unexpected adverse events believed to be associated with Regranex can be reported to the manufacturer at 888-734-7263 or online with the Food and Drug Administration MedWatch program at www.fda.gov/medwatch/report.htm.

Information about the increased risk of cancer-related deaths in patients who have used three or more tubes of becaplermin is now included in a boxed warning on the label of the diabetic foot and leg ulcer treatment.

On June 6, the Food and Drug Administration announced that the warning had been added to the label of becaplermin (Regranex), a recombinant human platelet-derived growth factor that was approved in 1997. It is marketed as Regranex Gel 0.01% for treating nonhealing diabetic leg and foot ulcers.

The boxed warning says that the increased risk of mortality was observed in a postmarketing retrospective cohort study in patients who had been treated with three or more tubes, and advises that Regranex gel should only be used “when the benefits can be expected to outweigh the risks.” The warning also says that it should be used “with caution” in patients with a known malignancy.

The retrospective study compared cancer incidence and cancer mortality among 1,622 patients who had been treated with Regranex to 2,809 similar patients who had not been treated with Regranex. The study found that the incidence of cancer was not increased among those in the Regranex group, but the risk of cancer mortality was five times higher among those patients who had been exposed to three or more tubes of Regranex.

“No single type of cancer was identified, but rather deaths from all types of cancer combined were observed,” according to the FDA's statement announcing the change in the label.

In March, the FDA announced that it was conducting a safety review of Regranex after receiving information about the epidemiologic study, and that labeling changes were possible. The changes in the label also are explained in a “Dear Healthcare Professional” letter issued by the manufacturer, Ortho-McNeil.

Because it is a growth factor and promotes cellular proliferation and angiogenesis, the manufacturer of Regranex has monitored patients treated with the product for an increased risk of cancer or other adverse effects in postapproval safety studies.

A long-term safety study which was completed in 2001 found that cancer-related deaths were higher among patients who had used Regranex than among those patients who had not used it, according to the FDA statement. This was followed by the retrospective study, which compared cancer rates and overall cancer mortality among patients with similar diagnoses and drug use in a medical claims database.

The rate of deaths from all cancers among the patients who had been treated with three or more tubes of Regranex was 3.9 per 1,000 person-years, compared with 0.9 per 1,000 person-years among the comparators, an adjusted rate ratio of 5.2, according to the Ortho-McNeil letter. (The rate ratio was adjusted for several possible confounders.)

The letter points out that the results “were consistent with no overall increase in cancer incidence” among the patients who had been exposed to the Regranex diabetic ulcer treatment: The rate of all cancers was 10.2 per 1,000 person-years among those patients who were treated with Regranex, compared with 9.1 per 1,000 person-years among the comparators for a 1.2 adjusted rate ratio. The “types of cancers were varied and were remote from the site of treatment,” the company said in its letter.

A Web link to the FDA's update and a link to the manufacturer's letter can be accessed at www.fda.gov/cder/drug/infopage/becaplermin/default.htm

Any serious or unexpected adverse events believed to be associated with Regranex can be reported to the manufacturer at 888-734-7263 or online with the Food and Drug Administration MedWatch program at www.fda.gov/medwatch/report.htm.

BELTSVILLE, MD. — A boxed warning about an increased suicidality risk with the use of antiepileptic drugs should not be added to the labels of drugs in this class, but patients prescribed these drugs should receive information about this risk with every prescription, according to the majority of two federal advisory panels.

At a joint meeting of two Food and Drug Administration advisory committees, panel members agreed with evidence indicating an increased suicidality risk, but voted 14-4 with 3 abstentions against a proposal to include it in a black box warning in the labels of all antiepileptic drugs (AEDs). However, most (17-4) voted that patients should receive a medication guide describing the finding with each AED prescription filled.

Among panelists' concerns was that a black box could reduce appropriate prescribing of AEDs and affect compliance. Dr. Daniel Pine, chief of child and adolescent research at the National Institute of Mental Health's mood and anxiety disorders program, Bethesda, Md., advised the FDA to come up with “creative ways, short of a black box” to communicate this information.

The panels reviewed the results of an FDA analysis of data on 11 AEDs that compared the rates of suicidality (episodes of suicidal ideation, suicidal behavior, or completed suicide) between patients in treatment and placebo groups. In a meta-analysis of 199 prospective, randomized, parallel-arm, placebo-controlled trials of 27,863 patients on treatment and 16,029 on placebo, the overall odds ratio for suicidality with treatment was a statistically significant 1.80. Odds ratios for individual AEDs ranged from 0.57 to 2.75. There were four completed suicides among people on treatment (0.1%), and none among those on placebo, and the rate of suicidal behavior or ideation was 0.37% among patients on an AED, and 0.24% among those on placebo.

The AEDs in the meta-analysis were carbamazepine (Carbatrol, Equetro), divalproex sodium (Depakote, Depakote ER), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran). Of the 199 trials, 31% evaluated AED use in epilepsy, 28% were for AED use for 8 psychiatric indications, and 41% were for 11 other indications.

When analyzed separately, odds ratios exceeded 1 (indicating an increased risk) for all but 3 of the 11 AEDs. The odds ratio was under 1 for carbamazepine, which had the second fewest patients in studies; and for divalproex; an odds ratio for felbamate could not be calculated because there were not many patients in the trials and there were no suicidality events among patients on placebo or the drug.

“We're quite comfortable saying there's causality between suicidality and AEDs,” Dr. Russell Katz, director of the FDA's division of neurology products, said. The signal was detected across different mechanisms of action, and appeared to be independent of the AED's mechanism.

The statisticians on the panel agreed that the analyses were solid. This is “a signal that is an important one for the field to be aware of,” said Andrew Leon, Ph.D., professor of biostatistics in psychiatry, Weill Cornell Medical Center, New York. He and another statistician were among those in favor of the black box.

The panels agreed in a 20-0 vote with 1 abstention that an overall increase in suicidality was shown for the AEDs analyzed, and most agreed (15-5 with one abstention) that this finding should apply to all currently approved, chronically administered AEDs. Dr. Katz said the FDA had proposed applying the warning to all marketed AEDs because limiting the warning to the 11 in the meta-analysis could shift prescribing to others.

During an open public hearing, representatives of the American Epilepsy Society, the American Academy of Neurology, and the Epilepsy Society expressed concerns that a black box warning about suicidality in AED labels could affect patient compliance.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

BELTSVILLE, MD. — A boxed warning about an increased suicidality risk with the use of antiepileptic drugs should not be added to the labels of drugs in this class, but patients prescribed these drugs should receive information about this risk with every prescription, according to the majority of two federal advisory panels.

At a joint meeting of two Food and Drug Administration advisory committees, panel members agreed with evidence indicating an increased suicidality risk, but voted 14-4 with 3 abstentions against a proposal to include it in a black box warning in the labels of all antiepileptic drugs (AEDs). However, most (17-4) voted that patients should receive a medication guide describing the finding with each AED prescription filled.

Among panelists' concerns was that a black box could reduce appropriate prescribing of AEDs and affect compliance. Dr. Daniel Pine, chief of child and adolescent research at the National Institute of Mental Health's mood and anxiety disorders program, Bethesda, Md., advised the FDA to come up with “creative ways, short of a black box” to communicate this information.

The panels reviewed the results of an FDA analysis of data on 11 AEDs that compared the rates of suicidality (episodes of suicidal ideation, suicidal behavior, or completed suicide) between patients in treatment and placebo groups. In a meta-analysis of 199 prospective, randomized, parallel-arm, placebo-controlled trials of 27,863 patients on treatment and 16,029 on placebo, the overall odds ratio for suicidality with treatment was a statistically significant 1.80. Odds ratios for individual AEDs ranged from 0.57 to 2.75. There were four completed suicides among people on treatment (0.1%), and none among those on placebo, and the rate of suicidal behavior or ideation was 0.37% among patients on an AED, and 0.24% among those on placebo.

The AEDs in the meta-analysis were carbamazepine (Carbatrol, Equetro), divalproex sodium (Depakote, Depakote ER), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran). Of the 199 trials, 31% evaluated AED use in epilepsy, 28% were for AED use for 8 psychiatric indications, and 41% were for 11 other indications.

When analyzed separately, odds ratios exceeded 1 (indicating an increased risk) for all but 3 of the 11 AEDs. The odds ratio was under 1 for carbamazepine, which had the second fewest patients in studies; and for divalproex; an odds ratio for felbamate could not be calculated because there were not many patients in the trials and there were no suicidality events among patients on placebo or the drug.

“We're quite comfortable saying there's causality between suicidality and AEDs,” Dr. Russell Katz, director of the FDA's division of neurology products, said. The signal was detected across different mechanisms of action, and appeared to be independent of the AED's mechanism.

The statisticians on the panel agreed that the analyses were solid. This is “a signal that is an important one for the field to be aware of,” said Andrew Leon, Ph.D., professor of biostatistics in psychiatry, Weill Cornell Medical Center, New York. He and another statistician were among those in favor of the black box.

The panels agreed in a 20-0 vote with 1 abstention that an overall increase in suicidality was shown for the AEDs analyzed, and most agreed (15-5 with one abstention) that this finding should apply to all currently approved, chronically administered AEDs. Dr. Katz said the FDA had proposed applying the warning to all marketed AEDs because limiting the warning to the 11 in the meta-analysis could shift prescribing to others.

During an open public hearing, representatives of the American Epilepsy Society, the American Academy of Neurology, and the Epilepsy Society expressed concerns that a black box warning about suicidality in AED labels could affect patient compliance.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

BELTSVILLE, MD. — A boxed warning about an increased suicidality risk with the use of antiepileptic drugs should not be added to the labels of drugs in this class, but patients prescribed these drugs should receive information about this risk with every prescription, according to the majority of two federal advisory panels.

At a joint meeting of two Food and Drug Administration advisory committees, panel members agreed with evidence indicating an increased suicidality risk, but voted 14-4 with 3 abstentions against a proposal to include it in a black box warning in the labels of all antiepileptic drugs (AEDs). However, most (17-4) voted that patients should receive a medication guide describing the finding with each AED prescription filled.

Among panelists' concerns was that a black box could reduce appropriate prescribing of AEDs and affect compliance. Dr. Daniel Pine, chief of child and adolescent research at the National Institute of Mental Health's mood and anxiety disorders program, Bethesda, Md., advised the FDA to come up with “creative ways, short of a black box” to communicate this information.

The panels reviewed the results of an FDA analysis of data on 11 AEDs that compared the rates of suicidality (episodes of suicidal ideation, suicidal behavior, or completed suicide) between patients in treatment and placebo groups. In a meta-analysis of 199 prospective, randomized, parallel-arm, placebo-controlled trials of 27,863 patients on treatment and 16,029 on placebo, the overall odds ratio for suicidality with treatment was a statistically significant 1.80. Odds ratios for individual AEDs ranged from 0.57 to 2.75. There were four completed suicides among people on treatment (0.1%), and none among those on placebo, and the rate of suicidal behavior or ideation was 0.37% among patients on an AED, and 0.24% among those on placebo.

The AEDs in the meta-analysis were carbamazepine (Carbatrol, Equetro), divalproex sodium (Depakote, Depakote ER), felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran). Of the 199 trials, 31% evaluated AED use in epilepsy, 28% were for AED use for 8 psychiatric indications, and 41% were for 11 other indications.

When analyzed separately, odds ratios exceeded 1 (indicating an increased risk) for all but 3 of the 11 AEDs. The odds ratio was under 1 for carbamazepine, which had the second fewest patients in studies; and for divalproex; an odds ratio for felbamate could not be calculated because there were not many patients in the trials and there were no suicidality events among patients on placebo or the drug.

“We're quite comfortable saying there's causality between suicidality and AEDs,” Dr. Russell Katz, director of the FDA's division of neurology products, said. The signal was detected across different mechanisms of action, and appeared to be independent of the AED's mechanism.

The statisticians on the panel agreed that the analyses were solid. This is “a signal that is an important one for the field to be aware of,” said Andrew Leon, Ph.D., professor of biostatistics in psychiatry, Weill Cornell Medical Center, New York. He and another statistician were among those in favor of the black box.

The panels agreed in a 20-0 vote with 1 abstention that an overall increase in suicidality was shown for the AEDs analyzed, and most agreed (15-5 with one abstention) that this finding should apply to all currently approved, chronically administered AEDs. Dr. Katz said the FDA had proposed applying the warning to all marketed AEDs because limiting the warning to the 11 in the meta-analysis could shift prescribing to others.

During an open public hearing, representatives of the American Epilepsy Society, the American Academy of Neurology, and the Epilepsy Society expressed concerns that a black box warning about suicidality in AED labels could affect patient compliance.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

A significant association between low bone mass and the presence of bone erosions in patients with psoriatic arthritis suggests there is a relationship between the two in these patients.

Though osteoclasts play a role in both, the relationship between erosions and bone mass in PsA is poorly understood.

Dr. Allen Anandarajah, of the allergy, immunology, and rheumatology unit at the University of Rochester, New York, evaluated data on 1,456 patients with the disease from the Consortium of Rheumatology Researchers of North America (CORRONA) database. “We found the people who had erosions were more likely to have low bone mass,” compared with those who don't have erosions, Dr. Anandarajah said at the annual European Congress of Rheumatology.

The study looked at the association between T scores at the lumbar spine and the presence or absence of erosions, adjusting for steroid use, gender, methotrexate use, other disease-modifying antirheumatic drug use, and the use of biologics, as well as for weight, age, body mass index, and disease index.

Of the patients, 567 (40%) had erosions and 889 (60%) had no erosions. The mean age of patients with erosions was 42 years, significantly younger than the patients with none, whose mean age was 45. Significantly more men (51.5%) had erosions than did women (48.5%).

The association between the presence of bone erosions and lower T scores of the lumbar spine was significant, with significantly lower T scores of the lumbar spine among patients with erosions, compared with those who had no erosions. (Focal erosions could be anywhere, he said, noting that the patients in the database usually had x-rays of the hands and feet. But the database includes information on any x-ray that revealed an erosion.)

“These patients do have low bone mass and … the mechanism between erosions and generalized bone loss or osteoporosis could be a common factor,” Dr. Anandarajah said.

A significant association between low bone mass and the presence of bone erosions in patients with psoriatic arthritis suggests there is a relationship between the two in these patients.

Though osteoclasts play a role in both, the relationship between erosions and bone mass in PsA is poorly understood.

Dr. Allen Anandarajah, of the allergy, immunology, and rheumatology unit at the University of Rochester, New York, evaluated data on 1,456 patients with the disease from the Consortium of Rheumatology Researchers of North America (CORRONA) database. “We found the people who had erosions were more likely to have low bone mass,” compared with those who don't have erosions, Dr. Anandarajah said at the annual European Congress of Rheumatology.

The study looked at the association between T scores at the lumbar spine and the presence or absence of erosions, adjusting for steroid use, gender, methotrexate use, other disease-modifying antirheumatic drug use, and the use of biologics, as well as for weight, age, body mass index, and disease index.

Of the patients, 567 (40%) had erosions and 889 (60%) had no erosions. The mean age of patients with erosions was 42 years, significantly younger than the patients with none, whose mean age was 45. Significantly more men (51.5%) had erosions than did women (48.5%).

The association between the presence of bone erosions and lower T scores of the lumbar spine was significant, with significantly lower T scores of the lumbar spine among patients with erosions, compared with those who had no erosions. (Focal erosions could be anywhere, he said, noting that the patients in the database usually had x-rays of the hands and feet. But the database includes information on any x-ray that revealed an erosion.)

“These patients do have low bone mass and … the mechanism between erosions and generalized bone loss or osteoporosis could be a common factor,” Dr. Anandarajah said.

A significant association between low bone mass and the presence of bone erosions in patients with psoriatic arthritis suggests there is a relationship between the two in these patients.

Though osteoclasts play a role in both, the relationship between erosions and bone mass in PsA is poorly understood.

Dr. Allen Anandarajah, of the allergy, immunology, and rheumatology unit at the University of Rochester, New York, evaluated data on 1,456 patients with the disease from the Consortium of Rheumatology Researchers of North America (CORRONA) database. “We found the people who had erosions were more likely to have low bone mass,” compared with those who don't have erosions, Dr. Anandarajah said at the annual European Congress of Rheumatology.

The study looked at the association between T scores at the lumbar spine and the presence or absence of erosions, adjusting for steroid use, gender, methotrexate use, other disease-modifying antirheumatic drug use, and the use of biologics, as well as for weight, age, body mass index, and disease index.

Of the patients, 567 (40%) had erosions and 889 (60%) had no erosions. The mean age of patients with erosions was 42 years, significantly younger than the patients with none, whose mean age was 45. Significantly more men (51.5%) had erosions than did women (48.5%).

The association between the presence of bone erosions and lower T scores of the lumbar spine was significant, with significantly lower T scores of the lumbar spine among patients with erosions, compared with those who had no erosions. (Focal erosions could be anywhere, he said, noting that the patients in the database usually had x-rays of the hands and feet. But the database includes information on any x-ray that revealed an erosion.)

“These patients do have low bone mass and … the mechanism between erosions and generalized bone loss or osteoporosis could be a common factor,” Dr. Anandarajah said.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

Intrapartum-related perinatal mortality risks have fallen, but not among women who attempt to undergo home birth, according to an analysis of birth data in England and Wales between 1994 and 2003.

The analysis, which the researchers stressed had “substantial limitations and should be treated with caution,” indicated that although the intrapartum-related perinatal mortality (IPPM) rate overall was generally low among the women who “booked” or intended to have a home birth, IPPM rates were significantly higher in subsets of women who attempted to give birth at home.

The findings were reported in the April 2 issue of BJOG: An International Journal of Obstetrics and Gynaecology.

The rate of IPPM (defined as deaths from intrapartum “asphyxia,” “anoxia,” or “trauma,” and including stillbirths and deaths that occurred in the first week) was highest among the women who planned to have a home birth but had to transfer their care to a hospital during pregnancy or labor, wrote Dr. Rintaro Mori and associates at the National Collaborating Centre for Women's and Children's Health, London.

Overall, 4,991 intrapartum perinatal deaths occurred among 6,314,315 births. The IPPM rate was 0.79 per 1,000 births, compared with 0.96 per 1,000 actual home births (intended and unintended home births combined) and 1.28 per 1,000 intended home births (those who completed a home birth or had planned to deliver at home but had to transfer).

They also looked at the IPPM rate in three subgroups. The rate was 0.48 per 1,000 births among those who intended to have home birth and completed it at home, compared with 6.05 per 1,000 births among those who planned to have a home birth but transferred their care to a hospital and 1.24 per 1,000 births among those who did not intend to have a home birth (BJOG 2008;115:554–8).

“Although the women who had intended to give birth at home and did so had a generally good outcome, those requiring transfer of care appeared to do significantly worse,” with IPPM rates “well in excess of the overall rate,” the authors observed, noting that they could not determine whether the women had been transferred during pregnancy or at the onset of labor.

The investigators speculated that the improvement in overall IPPM rates might have been due to improvements in clinical care.

The authors listed limitations of the study, including selection bias and potential confounding factors, such as the likelihood that women with risk factors would be advised to plan a hospital birth.

Ideally, they wrote, it would be best to compare the IPPM rates for women who planned a home birth to women at the same risk level who planned to deliver in the hospital, but these data are not available.

The results “certainly indicate the need for further prospective research to evaluate the relative safety of home birth,” they wrote, adding that it was “vital” to collect data prospectively to accurately determine intended and unintended home birth rates, and when and why transfer to a hospital takes place.

Dr. Mori, the lead author of the study, is now at the Osaka (Japan) Medical Center and Research Institute for Maternal and Child Health.

The alert, including information for patients, is on the FDA Web site at www.fda.gov/cder/drug/infopage/mycophenolate/default.htm

Rheumatologists who have been using mycophenolate mofetil off label to treat lupus and rheumatoid arthritis in women of reproductive age should be aware that the Food and Drug Administration has issued an alert about cases of birth defects and spontaneous abortions associated with its use in the first-trimester.

Mycophenolate mofetil—CellCept—is also used off label in women with erythema multiforme. The FDA's report concerns a second drug: Myfortic (mycophenolic acid). Mycophenolate mofetil (MMF) is an ester of the metabolite mycophenolic acid (MPA), which is the active drug substance in Myfortic. Both agents are approved to prevent organ rejection after transplantation.

The information about early pregnancy loss and congenital malformations was described in a letter to health care professionals and added to the black box warning in the labels of the two drugs in November 2007, when they were reclassified as pregnancy category D drugs. A classification of category D means there is positive evidence of human fetal risk, but potential benefits might warrant the use of the drug during pregnancy anyway. The drugs previously were classified as category C, meaning they were shown to be teratogenic or to have embryocidal effects in animals, but that there are no human data.

Now, published and unpublished reports associate the drugs with an increased risk of spontaneous abortions and serious congenital malformations in humans, including bilateral microtia or anotia, sometimes with atresia of the external auditory canals; oral clefts; and other major structural malformations, according to the FDA. In most cases, the mothers were taking MMF after an organ transplant, but in some cases, the women were taking MMF for systemic lupus erythematosus, erythema multiforme, or other immune-mediated conditions.

The data include 33 pregnancies exposed to MMF in 24 transplant patients in the National Transplantation Pregnancy Registry. There were 15 spontaneous abortions (45%). Of the 18 live-born infants, four (22%) had a major structural malformation. This is compared with the 3% background rate of congenital anomalies in the United States, and a rate of 4%–5% among babies born to women in the registry who took other immunosuppressive drugs. The FDA cited postmarketing data in 77 women exposed to MMF during pregnancy between 1995 and 2007: 25 had a spontaneous abortion and 14 had a malformed infant or fetus (including ear abnormalities in six cases).

The FDA is advising health care professionals to counsel women of childbearing potential about the fetal risks associated with taking the medications, and about contraceptive options. Health care professionals should not start treatment until they confirm patients are not pregnant, using a serum or urine pregnancy test that has a sensitivity of at least 25 mIU/mL, within 1 week of starting treatment.

“If therapy is initiated in a patient who is already pregnant or the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the developing fetus,” according to the FDA. “Women taking CellCept and Myfortic and who are planning to become pregnant should also talk with their doctors about the risks involved and whether alternative immunosuppressive agents can be considered,” according to the release.

The alert, including information for patients, is on the FDA Web site at www.fda.gov/cder/drug/infopage/mycophenolate/default.htm

Rheumatologists who have been using mycophenolate mofetil off label to treat lupus and rheumatoid arthritis in women of reproductive age should be aware that the Food and Drug Administration has issued an alert about cases of birth defects and spontaneous abortions associated with its use in the first-trimester.

Mycophenolate mofetil—CellCept—is also used off label in women with erythema multiforme. The FDA's report concerns a second drug: Myfortic (mycophenolic acid). Mycophenolate mofetil (MMF) is an ester of the metabolite mycophenolic acid (MPA), which is the active drug substance in Myfortic. Both agents are approved to prevent organ rejection after transplantation.

The information about early pregnancy loss and congenital malformations was described in a letter to health care professionals and added to the black box warning in the labels of the two drugs in November 2007, when they were reclassified as pregnancy category D drugs. A classification of category D means there is positive evidence of human fetal risk, but potential benefits might warrant the use of the drug during pregnancy anyway. The drugs previously were classified as category C, meaning they were shown to be teratogenic or to have embryocidal effects in animals, but that there are no human data.

Now, published and unpublished reports associate the drugs with an increased risk of spontaneous abortions and serious congenital malformations in humans, including bilateral microtia or anotia, sometimes with atresia of the external auditory canals; oral clefts; and other major structural malformations, according to the FDA. In most cases, the mothers were taking MMF after an organ transplant, but in some cases, the women were taking MMF for systemic lupus erythematosus, erythema multiforme, or other immune-mediated conditions.

The data include 33 pregnancies exposed to MMF in 24 transplant patients in the National Transplantation Pregnancy Registry. There were 15 spontaneous abortions (45%). Of the 18 live-born infants, four (22%) had a major structural malformation. This is compared with the 3% background rate of congenital anomalies in the United States, and a rate of 4%–5% among babies born to women in the registry who took other immunosuppressive drugs. The FDA cited postmarketing data in 77 women exposed to MMF during pregnancy between 1995 and 2007: 25 had a spontaneous abortion and 14 had a malformed infant or fetus (including ear abnormalities in six cases).

The FDA is advising health care professionals to counsel women of childbearing potential about the fetal risks associated with taking the medications, and about contraceptive options. Health care professionals should not start treatment until they confirm patients are not pregnant, using a serum or urine pregnancy test that has a sensitivity of at least 25 mIU/mL, within 1 week of starting treatment.

“If therapy is initiated in a patient who is already pregnant or the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the developing fetus,” according to the FDA. “Women taking CellCept and Myfortic and who are planning to become pregnant should also talk with their doctors about the risks involved and whether alternative immunosuppressive agents can be considered,” according to the release.

The alert, including information for patients, is on the FDA Web site at www.fda.gov/cder/drug/infopage/mycophenolate/default.htm

Rheumatologists who have been using mycophenolate mofetil off label to treat lupus and rheumatoid arthritis in women of reproductive age should be aware that the Food and Drug Administration has issued an alert about cases of birth defects and spontaneous abortions associated with its use in the first-trimester.

Mycophenolate mofetil—CellCept—is also used off label in women with erythema multiforme. The FDA's report concerns a second drug: Myfortic (mycophenolic acid). Mycophenolate mofetil (MMF) is an ester of the metabolite mycophenolic acid (MPA), which is the active drug substance in Myfortic. Both agents are approved to prevent organ rejection after transplantation.

The information about early pregnancy loss and congenital malformations was described in a letter to health care professionals and added to the black box warning in the labels of the two drugs in November 2007, when they were reclassified as pregnancy category D drugs. A classification of category D means there is positive evidence of human fetal risk, but potential benefits might warrant the use of the drug during pregnancy anyway. The drugs previously were classified as category C, meaning they were shown to be teratogenic or to have embryocidal effects in animals, but that there are no human data.

Now, published and unpublished reports associate the drugs with an increased risk of spontaneous abortions and serious congenital malformations in humans, including bilateral microtia or anotia, sometimes with atresia of the external auditory canals; oral clefts; and other major structural malformations, according to the FDA. In most cases, the mothers were taking MMF after an organ transplant, but in some cases, the women were taking MMF for systemic lupus erythematosus, erythema multiforme, or other immune-mediated conditions.

The data include 33 pregnancies exposed to MMF in 24 transplant patients in the National Transplantation Pregnancy Registry. There were 15 spontaneous abortions (45%). Of the 18 live-born infants, four (22%) had a major structural malformation. This is compared with the 3% background rate of congenital anomalies in the United States, and a rate of 4%–5% among babies born to women in the registry who took other immunosuppressive drugs. The FDA cited postmarketing data in 77 women exposed to MMF during pregnancy between 1995 and 2007: 25 had a spontaneous abortion and 14 had a malformed infant or fetus (including ear abnormalities in six cases).

The FDA is advising health care professionals to counsel women of childbearing potential about the fetal risks associated with taking the medications, and about contraceptive options. Health care professionals should not start treatment until they confirm patients are not pregnant, using a serum or urine pregnancy test that has a sensitivity of at least 25 mIU/mL, within 1 week of starting treatment.

“If therapy is initiated in a patient who is already pregnant or the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the developing fetus,” according to the FDA. “Women taking CellCept and Myfortic and who are planning to become pregnant should also talk with their doctors about the risks involved and whether alternative immunosuppressive agents can be considered,” according to the release.