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FDA warns about magnesium sulfate effects on newborns
Magnesium sulfate should not be used for more than 5-7 days in pregnant women in preterm labor, because in utero exposure may lead to hypocalcemia and an increased risk of osteopenia and bone fractures in newborns, the Food and Drug Administration announced May 30.
"The shortest duration of treatment that can result in harm to the baby is not known," the FDA stated.
The warning is based on epidemiologic studies that were mostly retrospective chart reviews, as well as 18 cases of newborns with skeletal anomalies whose mothers had been treated with magnesium sulfate for tocolysis. The cases had been reported to the FDA’s Adverse Event Reporting System (AERS) and were in the medical literature.
In these cases, exposure ranged from 8-12 weeks (average was almost 10 weeks), for an estimated average total maternal dose of 3,700 grams.
The newborns developed osteopenia-related skeletal anomalies, and some had multiple fractures of the ribs and long bones. The osteopenia and fractures were transient and had resolved in cases where the outcome was reported, according to the FDA.
Based on cases in the literature, "it is plausible that bone abnormalities in neonates are associated with prolonged in utero exposure to magnesium sulfate," since hypermagnesemia can cause hypocalcemia in the developing fetus, the FDA concluded.
Dr. Jeffrey Ecker, a high-risk obstetrician at Massachusetts General Hospital (MGH), Boston, said that this warning should not have an impact on practice because the length of exposure and maternal dose of magnesium sulfate cited in the FDA's statement are not recommended. The warning refers to cases of adverse outcomes in which magnesium sulfate was used for weeks at a time, which he said "would be unusual."
Magnesium sulfate is currently used to reduce the risk of cerebral palsy when premature delivery is anticipated, particularly at less than 32 weeks, and to reduce the risk of seizures in women with preeclampsia, two indications where there is good evidence that the use of magnesium sulfate improves outcomes, he noted in an interview.
There is much less evidence that it improves outcomes for the third use, as tocolysis, to delay delivery for 48 hours to allow for administration of steroids in women in preterm labor, said Dr. Ecker, also director of the maternal Fetal Medicine Fellowship at MGH and vice-chair of the American College of Obstetricians and Gynecologists' committee on obstetric practice. "But all three of those uses focus on very short term periods of exposure," he emphasized.*
The FDA is switching magnesium sulfate from a pregnancy category A (drugs for which adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester, and no evidence of risk in later trimesters) to pregnancy category D (drugs for which there is evidence of human fetal risks, but also potential benefits in pregnant women that may be acceptable in certain situations, despite the risks).
In addition to the new pregnancy category, the label for magnesium sulfate injection USP 50% will also have a new warning about these risks when administered for more than 5-7 days. There will be a new "labor and delivery" section pointing out that magnesium sulfate is not approved for treatment of preterm labor, the safety and efficacy of use for this indication "are not established," and "when used in pregnant women for conditions other than its approved indication, magnesium sulfate injection should be administered only by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities."
Magnesium sulfate is FDA approved to prevent seizures in preeclampsia.
Serious adverse events associated with this drug should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.
* Updated 6/5/2013
Magnesium sulfate should not be used for more than 5-7 days in pregnant women in preterm labor, because in utero exposure may lead to hypocalcemia and an increased risk of osteopenia and bone fractures in newborns, the Food and Drug Administration announced May 30.
"The shortest duration of treatment that can result in harm to the baby is not known," the FDA stated.
The warning is based on epidemiologic studies that were mostly retrospective chart reviews, as well as 18 cases of newborns with skeletal anomalies whose mothers had been treated with magnesium sulfate for tocolysis. The cases had been reported to the FDA’s Adverse Event Reporting System (AERS) and were in the medical literature.
In these cases, exposure ranged from 8-12 weeks (average was almost 10 weeks), for an estimated average total maternal dose of 3,700 grams.
The newborns developed osteopenia-related skeletal anomalies, and some had multiple fractures of the ribs and long bones. The osteopenia and fractures were transient and had resolved in cases where the outcome was reported, according to the FDA.
Based on cases in the literature, "it is plausible that bone abnormalities in neonates are associated with prolonged in utero exposure to magnesium sulfate," since hypermagnesemia can cause hypocalcemia in the developing fetus, the FDA concluded.
Dr. Jeffrey Ecker, a high-risk obstetrician at Massachusetts General Hospital (MGH), Boston, said that this warning should not have an impact on practice because the length of exposure and maternal dose of magnesium sulfate cited in the FDA's statement are not recommended. The warning refers to cases of adverse outcomes in which magnesium sulfate was used for weeks at a time, which he said "would be unusual."
Magnesium sulfate is currently used to reduce the risk of cerebral palsy when premature delivery is anticipated, particularly at less than 32 weeks, and to reduce the risk of seizures in women with preeclampsia, two indications where there is good evidence that the use of magnesium sulfate improves outcomes, he noted in an interview.
There is much less evidence that it improves outcomes for the third use, as tocolysis, to delay delivery for 48 hours to allow for administration of steroids in women in preterm labor, said Dr. Ecker, also director of the maternal Fetal Medicine Fellowship at MGH and vice-chair of the American College of Obstetricians and Gynecologists' committee on obstetric practice. "But all three of those uses focus on very short term periods of exposure," he emphasized.*
The FDA is switching magnesium sulfate from a pregnancy category A (drugs for which adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester, and no evidence of risk in later trimesters) to pregnancy category D (drugs for which there is evidence of human fetal risks, but also potential benefits in pregnant women that may be acceptable in certain situations, despite the risks).
In addition to the new pregnancy category, the label for magnesium sulfate injection USP 50% will also have a new warning about these risks when administered for more than 5-7 days. There will be a new "labor and delivery" section pointing out that magnesium sulfate is not approved for treatment of preterm labor, the safety and efficacy of use for this indication "are not established," and "when used in pregnant women for conditions other than its approved indication, magnesium sulfate injection should be administered only by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities."
Magnesium sulfate is FDA approved to prevent seizures in preeclampsia.
Serious adverse events associated with this drug should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.
* Updated 6/5/2013
Magnesium sulfate should not be used for more than 5-7 days in pregnant women in preterm labor, because in utero exposure may lead to hypocalcemia and an increased risk of osteopenia and bone fractures in newborns, the Food and Drug Administration announced May 30.
"The shortest duration of treatment that can result in harm to the baby is not known," the FDA stated.
The warning is based on epidemiologic studies that were mostly retrospective chart reviews, as well as 18 cases of newborns with skeletal anomalies whose mothers had been treated with magnesium sulfate for tocolysis. The cases had been reported to the FDA’s Adverse Event Reporting System (AERS) and were in the medical literature.
In these cases, exposure ranged from 8-12 weeks (average was almost 10 weeks), for an estimated average total maternal dose of 3,700 grams.
The newborns developed osteopenia-related skeletal anomalies, and some had multiple fractures of the ribs and long bones. The osteopenia and fractures were transient and had resolved in cases where the outcome was reported, according to the FDA.
Based on cases in the literature, "it is plausible that bone abnormalities in neonates are associated with prolonged in utero exposure to magnesium sulfate," since hypermagnesemia can cause hypocalcemia in the developing fetus, the FDA concluded.
Dr. Jeffrey Ecker, a high-risk obstetrician at Massachusetts General Hospital (MGH), Boston, said that this warning should not have an impact on practice because the length of exposure and maternal dose of magnesium sulfate cited in the FDA's statement are not recommended. The warning refers to cases of adverse outcomes in which magnesium sulfate was used for weeks at a time, which he said "would be unusual."
Magnesium sulfate is currently used to reduce the risk of cerebral palsy when premature delivery is anticipated, particularly at less than 32 weeks, and to reduce the risk of seizures in women with preeclampsia, two indications where there is good evidence that the use of magnesium sulfate improves outcomes, he noted in an interview.
There is much less evidence that it improves outcomes for the third use, as tocolysis, to delay delivery for 48 hours to allow for administration of steroids in women in preterm labor, said Dr. Ecker, also director of the maternal Fetal Medicine Fellowship at MGH and vice-chair of the American College of Obstetricians and Gynecologists' committee on obstetric practice. "But all three of those uses focus on very short term periods of exposure," he emphasized.*
The FDA is switching magnesium sulfate from a pregnancy category A (drugs for which adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester, and no evidence of risk in later trimesters) to pregnancy category D (drugs for which there is evidence of human fetal risks, but also potential benefits in pregnant women that may be acceptable in certain situations, despite the risks).
In addition to the new pregnancy category, the label for magnesium sulfate injection USP 50% will also have a new warning about these risks when administered for more than 5-7 days. There will be a new "labor and delivery" section pointing out that magnesium sulfate is not approved for treatment of preterm labor, the safety and efficacy of use for this indication "are not established," and "when used in pregnant women for conditions other than its approved indication, magnesium sulfate injection should be administered only by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities."
Magnesium sulfate is FDA approved to prevent seizures in preeclampsia.
Serious adverse events associated with this drug should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.
* Updated 6/5/2013
FDA approves two more drugs for advanced melanoma
Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.
Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.
Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.
Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.
The two drugs are not approved as combination treatment, according to a statement from the FDA.
The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.
"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.
In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).
The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.
In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.
Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.
The labels for both drugs warn that the drugs can cause fetal harm.
Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.
The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.
Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.
Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.
Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.
Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.
Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.
The two drugs are not approved as combination treatment, according to a statement from the FDA.
The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.
"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.
In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).
The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.
In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.
Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.
The labels for both drugs warn that the drugs can cause fetal harm.
Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.
The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.
Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.
Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.
Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.
Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.
Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.
The two drugs are not approved as combination treatment, according to a statement from the FDA.
The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.
"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.
In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).
The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.
In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.
Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.
The labels for both drugs warn that the drugs can cause fetal harm.
Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.
The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.
Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.
Familiar respiratory culprits fueled Alabama illnesses
A combination of influenza A, rhinovirus, and bacterial pneumonia – not avian influenza or a novel coronavirus – caused a cluster of serious respiratory illnesses that struck southeastern Alabama, according to state public health officials.
Testing that ruled out avian influenza and novel coronavirus for the cluster of cases, including some that were fatal, is “good news,” said State Health Officer Dr. Donald E. Williamson.
The state's department of health announced its findings in a statement issued May 23.
Earlier in May, seven people with unexplained fever, cough, and shortness of breath had been admitted to the hospital; two cases were fatal. Specimens in six of the seven patients were positive for influenza A, rhinovirus, or a combination of the two; and three patients had bacterial pneumonia, according to the statement. There were no pediatric cases; the ages of the patients ranged from the mid-20s to the 80s, a department spokesperson said.
Enhanced surveillance associated with the cluster of cases was no longer necessary, Dr. Mary McIntyre, assistant state health officer for disease control and prevention, said in the statement. But she encouraged health care providers “to continue routine year-round influenza surveillance activities and submit specimens to the state laboratory for testing.”
Influenza was most likely the main cause of the severe cases, infectious disease specialist Dr. William Schaffner said in an interview. The cluster illustrates that while influenza is a winter infection, it “remains capable of being transmitted and occurring in our population at very low levels” in the summer months, he cautioned.
The investigation of the Alabama cluster “reinforces the need for physicians to be alert constantly, to treat serious disease with respect, get those specimens and, in circumstances like this, at a drop of the hat, notify the public health department,” added Dr. Schaffner, professor and chair of the department of preventive medicine at Vanderbilt University, Nashville, Tenn.
A combination of influenza A, rhinovirus, and bacterial pneumonia – not avian influenza or a novel coronavirus – caused a cluster of serious respiratory illnesses that struck southeastern Alabama, according to state public health officials.
Testing that ruled out avian influenza and novel coronavirus for the cluster of cases, including some that were fatal, is “good news,” said State Health Officer Dr. Donald E. Williamson.
The state's department of health announced its findings in a statement issued May 23.
Earlier in May, seven people with unexplained fever, cough, and shortness of breath had been admitted to the hospital; two cases were fatal. Specimens in six of the seven patients were positive for influenza A, rhinovirus, or a combination of the two; and three patients had bacterial pneumonia, according to the statement. There were no pediatric cases; the ages of the patients ranged from the mid-20s to the 80s, a department spokesperson said.
Enhanced surveillance associated with the cluster of cases was no longer necessary, Dr. Mary McIntyre, assistant state health officer for disease control and prevention, said in the statement. But she encouraged health care providers “to continue routine year-round influenza surveillance activities and submit specimens to the state laboratory for testing.”
Influenza was most likely the main cause of the severe cases, infectious disease specialist Dr. William Schaffner said in an interview. The cluster illustrates that while influenza is a winter infection, it “remains capable of being transmitted and occurring in our population at very low levels” in the summer months, he cautioned.
The investigation of the Alabama cluster “reinforces the need for physicians to be alert constantly, to treat serious disease with respect, get those specimens and, in circumstances like this, at a drop of the hat, notify the public health department,” added Dr. Schaffner, professor and chair of the department of preventive medicine at Vanderbilt University, Nashville, Tenn.
A combination of influenza A, rhinovirus, and bacterial pneumonia – not avian influenza or a novel coronavirus – caused a cluster of serious respiratory illnesses that struck southeastern Alabama, according to state public health officials.
Testing that ruled out avian influenza and novel coronavirus for the cluster of cases, including some that were fatal, is “good news,” said State Health Officer Dr. Donald E. Williamson.
The state's department of health announced its findings in a statement issued May 23.
Earlier in May, seven people with unexplained fever, cough, and shortness of breath had been admitted to the hospital; two cases were fatal. Specimens in six of the seven patients were positive for influenza A, rhinovirus, or a combination of the two; and three patients had bacterial pneumonia, according to the statement. There were no pediatric cases; the ages of the patients ranged from the mid-20s to the 80s, a department spokesperson said.
Enhanced surveillance associated with the cluster of cases was no longer necessary, Dr. Mary McIntyre, assistant state health officer for disease control and prevention, said in the statement. But she encouraged health care providers “to continue routine year-round influenza surveillance activities and submit specimens to the state laboratory for testing.”
Influenza was most likely the main cause of the severe cases, infectious disease specialist Dr. William Schaffner said in an interview. The cluster illustrates that while influenza is a winter infection, it “remains capable of being transmitted and occurring in our population at very low levels” in the summer months, he cautioned.
The investigation of the Alabama cluster “reinforces the need for physicians to be alert constantly, to treat serious disease with respect, get those specimens and, in circumstances like this, at a drop of the hat, notify the public health department,” added Dr. Schaffner, professor and chair of the department of preventive medicine at Vanderbilt University, Nashville, Tenn.
Panel supports lower doses of novel insomnia drug
SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel agreed that suvorexant, a drug for insomnia with a novel mechanism of action, was effective in improving the time it took to get to sleep, and for maintenance of sleep in elderly and younger adults. The panel also agreed that its safety profile was acceptable at the lower starting doses.
But at the May 22 meeting, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was divided on whether the higher doses recommended for people with inadequate responses on the starting doses were safe, because serious adverse events such as evidence of impaired driving and excessive daytime somnolence were increased at those doses.
The panel was not asked to vote on whether to recommend approval of the drug, which is being reviewed for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance. If approved, suvorexant, an orexin receptor antagonist, would be the first drug in this class to be approved for insomnia. The FDA usually follows the recommendations of its advisory panels.
The manufacturer, Merck Research Laboratories, studied the drug in almost 3,000 patients, including 1,784 in phase III studies, and has recommended doses of 20 mg (starting dose) up to 40 mg taken at bedtime for adults aged under 65 years, and 15 mg (starting dose) up to 30 mg for people aged 65 and older.
Suvorexant blocks the binding of orexin A and B neuropeptides to orexin receptors, "presumably inhibiting activation of neurons to the arousal system," according to the FDA.
Testing of suvorexant involved three phase III studies – two studies that compared the effects of higher and lower doses against placebo on the onset and maintenance of sleep over 3 months, and a 1-year safety study in a total of 2,809 patients, including 1,784 treated with suvorexant. The drug was effective in improving the onset of and maintenance of sleep, and was sustained for a year, according to the company. In the phase III studies, next-day somnolence was reported by 3% of those on placebo, compared with 7% and 11% of those on low and high doses of suvorexant, respectively. Excessive daytime sleepiness was reported by 0.2% of those on placebo, compared with 0.6% and 1.1%, of those on low and high doses, respectively.
The FDA raised concerns about next-day somnolence, suicidal ideation, impaired driving, and other potentially serious side effects of the drug that appeared to be dose related, and concluded that a dose below 15 mg would be preferable. "Suvorexant is effective but not safe at the higher doses mainly studied," said Dr. Ronald Farkas, clinical team leader in the division of neurology products at the FDA’s Center for Drug Evaluation and Research. The risk-benefit profile may be more favorable at lower doses, since lower doses have similar efficacy, and phase II data suggested that the 10-mg dose may be effective, he told the panel.
In a 16-0 vote with 1 abstention, the panel agreed that based on the clinical trial results, suvorexant was effective for sleep maintenance, and voted 12-4 with 1 abstention, that the drug was effective for improving sleep onset, reflecting less robust effects on this endpoint.
The panel voted 13-3 with 1 abstention that the starting doses were acceptably safe. But they voted 8-7 with 2 abstentions that the safety of the higher doses – 40 mg among those under age 65 and 30 mg among those aged 65 and older – were not acceptable.
"Even though I think the lower doses are probably safe, I have to assume that many patients are going to graduate up to the higher doses," said Dr. Robert Clancy, professor of neurology and pediatrics at the University of Pennsylvania, Philadelphia. Dr. Clancy voted that the safety of the higher doses was not acceptable. He cited the 1.1% rate of excessive daytime sleepiness associated with the higher dose as a particular concern, which he predicted would result in fatalities, although none occurred in trials.
Dr. Ronald Chervin, professor of neurology and director of the sleep disorders center at the University of Michigan, Ann Arbor, was among those who agreed that the higher doses were acceptable. "My gut feeling overall is that we’re not seeing anything different in terms of a dose response on the safety side ... than what we would see for any of the hypnotics that we are currently using," he said.
The company expects the FDA to take action on the drug by mid-year, and if approved, the drug will have to go through the drug scheduling process, the company said in a statement after the meeting.
Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.
SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel agreed that suvorexant, a drug for insomnia with a novel mechanism of action, was effective in improving the time it took to get to sleep, and for maintenance of sleep in elderly and younger adults. The panel also agreed that its safety profile was acceptable at the lower starting doses.
But at the May 22 meeting, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was divided on whether the higher doses recommended for people with inadequate responses on the starting doses were safe, because serious adverse events such as evidence of impaired driving and excessive daytime somnolence were increased at those doses.
The panel was not asked to vote on whether to recommend approval of the drug, which is being reviewed for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance. If approved, suvorexant, an orexin receptor antagonist, would be the first drug in this class to be approved for insomnia. The FDA usually follows the recommendations of its advisory panels.
The manufacturer, Merck Research Laboratories, studied the drug in almost 3,000 patients, including 1,784 in phase III studies, and has recommended doses of 20 mg (starting dose) up to 40 mg taken at bedtime for adults aged under 65 years, and 15 mg (starting dose) up to 30 mg for people aged 65 and older.
Suvorexant blocks the binding of orexin A and B neuropeptides to orexin receptors, "presumably inhibiting activation of neurons to the arousal system," according to the FDA.
Testing of suvorexant involved three phase III studies – two studies that compared the effects of higher and lower doses against placebo on the onset and maintenance of sleep over 3 months, and a 1-year safety study in a total of 2,809 patients, including 1,784 treated with suvorexant. The drug was effective in improving the onset of and maintenance of sleep, and was sustained for a year, according to the company. In the phase III studies, next-day somnolence was reported by 3% of those on placebo, compared with 7% and 11% of those on low and high doses of suvorexant, respectively. Excessive daytime sleepiness was reported by 0.2% of those on placebo, compared with 0.6% and 1.1%, of those on low and high doses, respectively.
The FDA raised concerns about next-day somnolence, suicidal ideation, impaired driving, and other potentially serious side effects of the drug that appeared to be dose related, and concluded that a dose below 15 mg would be preferable. "Suvorexant is effective but not safe at the higher doses mainly studied," said Dr. Ronald Farkas, clinical team leader in the division of neurology products at the FDA’s Center for Drug Evaluation and Research. The risk-benefit profile may be more favorable at lower doses, since lower doses have similar efficacy, and phase II data suggested that the 10-mg dose may be effective, he told the panel.
In a 16-0 vote with 1 abstention, the panel agreed that based on the clinical trial results, suvorexant was effective for sleep maintenance, and voted 12-4 with 1 abstention, that the drug was effective for improving sleep onset, reflecting less robust effects on this endpoint.
The panel voted 13-3 with 1 abstention that the starting doses were acceptably safe. But they voted 8-7 with 2 abstentions that the safety of the higher doses – 40 mg among those under age 65 and 30 mg among those aged 65 and older – were not acceptable.
"Even though I think the lower doses are probably safe, I have to assume that many patients are going to graduate up to the higher doses," said Dr. Robert Clancy, professor of neurology and pediatrics at the University of Pennsylvania, Philadelphia. Dr. Clancy voted that the safety of the higher doses was not acceptable. He cited the 1.1% rate of excessive daytime sleepiness associated with the higher dose as a particular concern, which he predicted would result in fatalities, although none occurred in trials.
Dr. Ronald Chervin, professor of neurology and director of the sleep disorders center at the University of Michigan, Ann Arbor, was among those who agreed that the higher doses were acceptable. "My gut feeling overall is that we’re not seeing anything different in terms of a dose response on the safety side ... than what we would see for any of the hypnotics that we are currently using," he said.
The company expects the FDA to take action on the drug by mid-year, and if approved, the drug will have to go through the drug scheduling process, the company said in a statement after the meeting.
Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.
SILVER SPRING, MD. – The majority of a Food and Drug Administration advisory panel agreed that suvorexant, a drug for insomnia with a novel mechanism of action, was effective in improving the time it took to get to sleep, and for maintenance of sleep in elderly and younger adults. The panel also agreed that its safety profile was acceptable at the lower starting doses.
But at the May 22 meeting, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee was divided on whether the higher doses recommended for people with inadequate responses on the starting doses were safe, because serious adverse events such as evidence of impaired driving and excessive daytime somnolence were increased at those doses.
The panel was not asked to vote on whether to recommend approval of the drug, which is being reviewed for the treatment of insomnia characterized by difficulties with sleep onset and/or maintenance. If approved, suvorexant, an orexin receptor antagonist, would be the first drug in this class to be approved for insomnia. The FDA usually follows the recommendations of its advisory panels.
The manufacturer, Merck Research Laboratories, studied the drug in almost 3,000 patients, including 1,784 in phase III studies, and has recommended doses of 20 mg (starting dose) up to 40 mg taken at bedtime for adults aged under 65 years, and 15 mg (starting dose) up to 30 mg for people aged 65 and older.
Suvorexant blocks the binding of orexin A and B neuropeptides to orexin receptors, "presumably inhibiting activation of neurons to the arousal system," according to the FDA.
Testing of suvorexant involved three phase III studies – two studies that compared the effects of higher and lower doses against placebo on the onset and maintenance of sleep over 3 months, and a 1-year safety study in a total of 2,809 patients, including 1,784 treated with suvorexant. The drug was effective in improving the onset of and maintenance of sleep, and was sustained for a year, according to the company. In the phase III studies, next-day somnolence was reported by 3% of those on placebo, compared with 7% and 11% of those on low and high doses of suvorexant, respectively. Excessive daytime sleepiness was reported by 0.2% of those on placebo, compared with 0.6% and 1.1%, of those on low and high doses, respectively.
The FDA raised concerns about next-day somnolence, suicidal ideation, impaired driving, and other potentially serious side effects of the drug that appeared to be dose related, and concluded that a dose below 15 mg would be preferable. "Suvorexant is effective but not safe at the higher doses mainly studied," said Dr. Ronald Farkas, clinical team leader in the division of neurology products at the FDA’s Center for Drug Evaluation and Research. The risk-benefit profile may be more favorable at lower doses, since lower doses have similar efficacy, and phase II data suggested that the 10-mg dose may be effective, he told the panel.
In a 16-0 vote with 1 abstention, the panel agreed that based on the clinical trial results, suvorexant was effective for sleep maintenance, and voted 12-4 with 1 abstention, that the drug was effective for improving sleep onset, reflecting less robust effects on this endpoint.
The panel voted 13-3 with 1 abstention that the starting doses were acceptably safe. But they voted 8-7 with 2 abstentions that the safety of the higher doses – 40 mg among those under age 65 and 30 mg among those aged 65 and older – were not acceptable.
"Even though I think the lower doses are probably safe, I have to assume that many patients are going to graduate up to the higher doses," said Dr. Robert Clancy, professor of neurology and pediatrics at the University of Pennsylvania, Philadelphia. Dr. Clancy voted that the safety of the higher doses was not acceptable. He cited the 1.1% rate of excessive daytime sleepiness associated with the higher dose as a particular concern, which he predicted would result in fatalities, although none occurred in trials.
Dr. Ronald Chervin, professor of neurology and director of the sleep disorders center at the University of Michigan, Ann Arbor, was among those who agreed that the higher doses were acceptable. "My gut feeling overall is that we’re not seeing anything different in terms of a dose response on the safety side ... than what we would see for any of the hypnotics that we are currently using," he said.
The company expects the FDA to take action on the drug by mid-year, and if approved, the drug will have to go through the drug scheduling process, the company said in a statement after the meeting.
Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.
FROM AN FDA ADVISORY PANEL MEETING
CDC report estimates one in five children have a mental disorder
Attention-deficit/hyperactivity disorder is the most prevalent mental disorder in children under aged 18 years in the United States, followed by depression, behavioral or conduct problems, anxiety, substance-use disorders, autism spectrum disorders, and Tourette syndrome, according to a report issued May 16 by the Centers for Disease Control and Prevention.
Millions of children in the United States have mental disorders, which are "a substantial public health concern with considerable associated costs to individuals, families, and society," concludes the report, titled "Mental Health Surveillance Among Children in the United States – 2005-2011." The report estimates that 20% of the children in the United States have mental disorders; the prevalence of mental disorders is increasing; and about $247 billion is spent on mental health in children annually.
This is the first CDC report to track the number of children (under age 18 years) in the United States who have a specific mental disorder, defined as "serious deviations from expected cognitive, social, and emotional development." The definition includes conditions that meet DSM-IV-TR criteria or criteria in the International Classification of Diseases. The report is published as a supplement to the May 17 Morbidity and Mortality Weekly Report (MMWR 2013;62 [Suppl. 2]:1-35).
"This is an important and helpful report," Dr. David Fassler, a child psychiatrist in Burlington, Vt., said in an interview. "Consistent with previous findings, it demonstrates that nearly one child in five has signs and symptoms of a significant psychiatric illness in any given year.
"The report also confirms that the prevalence of these disorders appears to be increasing, although the authors note that this finding may be due to changes in case definition, public perception, or policies regarding access to health care."
Furthermore, he predicted that the data in the report would be useful to parents, advocates, legislators, regulators. The findings "underscore the growing need for enhanced access to comprehensive mental health and substance abuse treatment services for children, adolescents and families," added Dr. Fassler, clinical professor of psychiatry, University of Vermont, Burlington.
The findings of the report were based on data from different national surveys and studies in the United States. The proportion of children affected by the outcomes studies varied by the condition, the survey and age group, the authors said, but they "begin to illustrate the impact of mental disorders among children."
Among the findings was that, in any given year, 13%-20% of children have a mental disorder. Among current diagnoses of mental disorders reported by parents of children aged 3-17 years, attention-deficit/hyperactivity disorder (ADHD) was the most common, at almost 7%. The next most common were behavioral or conduct problems (3.5%), anxiety (3%), depression (2.1%), autism spectrum disorders (ASDs) (1.1%), and Tourette syndrome (0.2% among children aged 6-17 years).
In addition, almost 5% of adolescents aged 12-17 years reported having an "illicit drug use disorder" in the past year, and 4.2% had an alcohol abuse disorder in the past year.
In 2010, suicide was the second-leading cause of death among children aged 12-17 years. Among people aged 10-19 years, the suicide rate was 4.5 suicides/100,000 people. About 8% of adolescents aged 12-17 years said that they had at least 14 "mentally unhealthy days in the past month."
The authors also found that all demographic groups were affected by mental disorders, but the estimated prevalence varied among racial and ethnic groups. For example, the prevalence of ADHD was lowest among Hispanic children and behavioral or conduct problems were the highest among black non-Hispanic children. ASDs "tended to be higher" among white non-Hispanic children, and white non-Hispanic children were affected by anxiety more than were black non-Hispanic children.
In addition, anxiety, ADHD, and ASD were more common among children who had health insurance.
The authors concluded that surveillance "is a critical first step in the public health approach to mental health among children," and that surveillance data "can help prioritize areas for research on risk and protective factors and provide empirical evidence to develop effective interventions that can prevent mental disorders and promote mental health."
The authors of the report are from the CDC, the Health Resources and Services Administration, the National Institute of Mental Health, and the Substance Abuse and Mental Health Services Administration.
The report complements a 2011 CDC report on mental illness in adults.
Attention-deficit/hyperactivity disorder is the most prevalent mental disorder in children under aged 18 years in the United States, followed by depression, behavioral or conduct problems, anxiety, substance-use disorders, autism spectrum disorders, and Tourette syndrome, according to a report issued May 16 by the Centers for Disease Control and Prevention.
Millions of children in the United States have mental disorders, which are "a substantial public health concern with considerable associated costs to individuals, families, and society," concludes the report, titled "Mental Health Surveillance Among Children in the United States – 2005-2011." The report estimates that 20% of the children in the United States have mental disorders; the prevalence of mental disorders is increasing; and about $247 billion is spent on mental health in children annually.
This is the first CDC report to track the number of children (under age 18 years) in the United States who have a specific mental disorder, defined as "serious deviations from expected cognitive, social, and emotional development." The definition includes conditions that meet DSM-IV-TR criteria or criteria in the International Classification of Diseases. The report is published as a supplement to the May 17 Morbidity and Mortality Weekly Report (MMWR 2013;62 [Suppl. 2]:1-35).
"This is an important and helpful report," Dr. David Fassler, a child psychiatrist in Burlington, Vt., said in an interview. "Consistent with previous findings, it demonstrates that nearly one child in five has signs and symptoms of a significant psychiatric illness in any given year.
"The report also confirms that the prevalence of these disorders appears to be increasing, although the authors note that this finding may be due to changes in case definition, public perception, or policies regarding access to health care."
Furthermore, he predicted that the data in the report would be useful to parents, advocates, legislators, regulators. The findings "underscore the growing need for enhanced access to comprehensive mental health and substance abuse treatment services for children, adolescents and families," added Dr. Fassler, clinical professor of psychiatry, University of Vermont, Burlington.
The findings of the report were based on data from different national surveys and studies in the United States. The proportion of children affected by the outcomes studies varied by the condition, the survey and age group, the authors said, but they "begin to illustrate the impact of mental disorders among children."
Among the findings was that, in any given year, 13%-20% of children have a mental disorder. Among current diagnoses of mental disorders reported by parents of children aged 3-17 years, attention-deficit/hyperactivity disorder (ADHD) was the most common, at almost 7%. The next most common were behavioral or conduct problems (3.5%), anxiety (3%), depression (2.1%), autism spectrum disorders (ASDs) (1.1%), and Tourette syndrome (0.2% among children aged 6-17 years).
In addition, almost 5% of adolescents aged 12-17 years reported having an "illicit drug use disorder" in the past year, and 4.2% had an alcohol abuse disorder in the past year.
In 2010, suicide was the second-leading cause of death among children aged 12-17 years. Among people aged 10-19 years, the suicide rate was 4.5 suicides/100,000 people. About 8% of adolescents aged 12-17 years said that they had at least 14 "mentally unhealthy days in the past month."
The authors also found that all demographic groups were affected by mental disorders, but the estimated prevalence varied among racial and ethnic groups. For example, the prevalence of ADHD was lowest among Hispanic children and behavioral or conduct problems were the highest among black non-Hispanic children. ASDs "tended to be higher" among white non-Hispanic children, and white non-Hispanic children were affected by anxiety more than were black non-Hispanic children.
In addition, anxiety, ADHD, and ASD were more common among children who had health insurance.
The authors concluded that surveillance "is a critical first step in the public health approach to mental health among children," and that surveillance data "can help prioritize areas for research on risk and protective factors and provide empirical evidence to develop effective interventions that can prevent mental disorders and promote mental health."
The authors of the report are from the CDC, the Health Resources and Services Administration, the National Institute of Mental Health, and the Substance Abuse and Mental Health Services Administration.
The report complements a 2011 CDC report on mental illness in adults.
Attention-deficit/hyperactivity disorder is the most prevalent mental disorder in children under aged 18 years in the United States, followed by depression, behavioral or conduct problems, anxiety, substance-use disorders, autism spectrum disorders, and Tourette syndrome, according to a report issued May 16 by the Centers for Disease Control and Prevention.
Millions of children in the United States have mental disorders, which are "a substantial public health concern with considerable associated costs to individuals, families, and society," concludes the report, titled "Mental Health Surveillance Among Children in the United States – 2005-2011." The report estimates that 20% of the children in the United States have mental disorders; the prevalence of mental disorders is increasing; and about $247 billion is spent on mental health in children annually.
This is the first CDC report to track the number of children (under age 18 years) in the United States who have a specific mental disorder, defined as "serious deviations from expected cognitive, social, and emotional development." The definition includes conditions that meet DSM-IV-TR criteria or criteria in the International Classification of Diseases. The report is published as a supplement to the May 17 Morbidity and Mortality Weekly Report (MMWR 2013;62 [Suppl. 2]:1-35).
"This is an important and helpful report," Dr. David Fassler, a child psychiatrist in Burlington, Vt., said in an interview. "Consistent with previous findings, it demonstrates that nearly one child in five has signs and symptoms of a significant psychiatric illness in any given year.
"The report also confirms that the prevalence of these disorders appears to be increasing, although the authors note that this finding may be due to changes in case definition, public perception, or policies regarding access to health care."
Furthermore, he predicted that the data in the report would be useful to parents, advocates, legislators, regulators. The findings "underscore the growing need for enhanced access to comprehensive mental health and substance abuse treatment services for children, adolescents and families," added Dr. Fassler, clinical professor of psychiatry, University of Vermont, Burlington.
The findings of the report were based on data from different national surveys and studies in the United States. The proportion of children affected by the outcomes studies varied by the condition, the survey and age group, the authors said, but they "begin to illustrate the impact of mental disorders among children."
Among the findings was that, in any given year, 13%-20% of children have a mental disorder. Among current diagnoses of mental disorders reported by parents of children aged 3-17 years, attention-deficit/hyperactivity disorder (ADHD) was the most common, at almost 7%. The next most common were behavioral or conduct problems (3.5%), anxiety (3%), depression (2.1%), autism spectrum disorders (ASDs) (1.1%), and Tourette syndrome (0.2% among children aged 6-17 years).
In addition, almost 5% of adolescents aged 12-17 years reported having an "illicit drug use disorder" in the past year, and 4.2% had an alcohol abuse disorder in the past year.
In 2010, suicide was the second-leading cause of death among children aged 12-17 years. Among people aged 10-19 years, the suicide rate was 4.5 suicides/100,000 people. About 8% of adolescents aged 12-17 years said that they had at least 14 "mentally unhealthy days in the past month."
The authors also found that all demographic groups were affected by mental disorders, but the estimated prevalence varied among racial and ethnic groups. For example, the prevalence of ADHD was lowest among Hispanic children and behavioral or conduct problems were the highest among black non-Hispanic children. ASDs "tended to be higher" among white non-Hispanic children, and white non-Hispanic children were affected by anxiety more than were black non-Hispanic children.
In addition, anxiety, ADHD, and ASD were more common among children who had health insurance.
The authors concluded that surveillance "is a critical first step in the public health approach to mental health among children," and that surveillance data "can help prioritize areas for research on risk and protective factors and provide empirical evidence to develop effective interventions that can prevent mental disorders and promote mental health."
The authors of the report are from the CDC, the Health Resources and Services Administration, the National Institute of Mental Health, and the Substance Abuse and Mental Health Services Administration.
The report complements a 2011 CDC report on mental illness in adults.
Major finding: Mental disorders affect as many as 13%-20% of children aged 17 years and younger in any given year, and are an important public health issue.
Data source: A CDC report providing estimates of the prevalence of mental health disorders among children under age 18 years, using data from national surveys and studies, including the National Survey of Children’s Health, and the National Health and Nutrition and Examination Survey.
Disclosures: The authors of the report are from the CDC, the Health Resources and Services Administration, the National Institute of Mental Health, and the Substance Abuse and Mental Health Services Administration.
Golimumab indication expanded to include ulcerative colitis
The approval of the biologic drug golimumab has been expanded to include the treatment of adults with moderate to severe ulcerative colitis that is refractory to prior treatment or requires continuous steroid therapy, the Food and Drug Administration announced on May 15.
Golimumab (Simponi), a tumor necrosis factor–blocker, was approved in 2009 for treatment of moderate to severe active rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all in adults. Simponi is marketed by Janssen Ortho Biotech.
The approval for ulcerative colitis was based on two studies of patients with moderate to severe ulcerative colitis, according to the FDA statement announcing the approval. In one study, which enrolled 513 patients who could not tolerate or had not responded to other treatments, "a greater proportion of Simponi-treated patients achieved clinical response, clinical remission and, as seen during endoscopy, had improved appearance of the colon after 6 weeks," compared with those on placebo, the statement said.
In a study of 310 patients who had responded to golimumab and were then randomized to continue treatment with golimumab or were switched to placebo, "a greater proportion of Simponi-treated patients maintained clinical response through week 54, had clinical remission at both weeks 30 and 54 and, as seen during endoscopy, had improved appearance of the colon at both weeks 30 and 54 compared with the placebo group," the FDA said. The most common adverse effects associated with golimumab are upper respiratory infection and redness at the injection site.
The risks of serious infections, invasive fungal infections, reactivation of hepatitis B infection, lymphoma, heart failure, nervous system disorders, and allergic reactions are increased with treatment.
Serious adverse events associated with golimumab should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch/.
The approval of the biologic drug golimumab has been expanded to include the treatment of adults with moderate to severe ulcerative colitis that is refractory to prior treatment or requires continuous steroid therapy, the Food and Drug Administration announced on May 15.
Golimumab (Simponi), a tumor necrosis factor–blocker, was approved in 2009 for treatment of moderate to severe active rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all in adults. Simponi is marketed by Janssen Ortho Biotech.
The approval for ulcerative colitis was based on two studies of patients with moderate to severe ulcerative colitis, according to the FDA statement announcing the approval. In one study, which enrolled 513 patients who could not tolerate or had not responded to other treatments, "a greater proportion of Simponi-treated patients achieved clinical response, clinical remission and, as seen during endoscopy, had improved appearance of the colon after 6 weeks," compared with those on placebo, the statement said.
In a study of 310 patients who had responded to golimumab and were then randomized to continue treatment with golimumab or were switched to placebo, "a greater proportion of Simponi-treated patients maintained clinical response through week 54, had clinical remission at both weeks 30 and 54 and, as seen during endoscopy, had improved appearance of the colon at both weeks 30 and 54 compared with the placebo group," the FDA said. The most common adverse effects associated with golimumab are upper respiratory infection and redness at the injection site.
The risks of serious infections, invasive fungal infections, reactivation of hepatitis B infection, lymphoma, heart failure, nervous system disorders, and allergic reactions are increased with treatment.
Serious adverse events associated with golimumab should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch/.
The approval of the biologic drug golimumab has been expanded to include the treatment of adults with moderate to severe ulcerative colitis that is refractory to prior treatment or requires continuous steroid therapy, the Food and Drug Administration announced on May 15.
Golimumab (Simponi), a tumor necrosis factor–blocker, was approved in 2009 for treatment of moderate to severe active rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, all in adults. Simponi is marketed by Janssen Ortho Biotech.
The approval for ulcerative colitis was based on two studies of patients with moderate to severe ulcerative colitis, according to the FDA statement announcing the approval. In one study, which enrolled 513 patients who could not tolerate or had not responded to other treatments, "a greater proportion of Simponi-treated patients achieved clinical response, clinical remission and, as seen during endoscopy, had improved appearance of the colon after 6 weeks," compared with those on placebo, the statement said.
In a study of 310 patients who had responded to golimumab and were then randomized to continue treatment with golimumab or were switched to placebo, "a greater proportion of Simponi-treated patients maintained clinical response through week 54, had clinical remission at both weeks 30 and 54 and, as seen during endoscopy, had improved appearance of the colon at both weeks 30 and 54 compared with the placebo group," the FDA said. The most common adverse effects associated with golimumab are upper respiratory infection and redness at the injection site.
The risks of serious infections, invasive fungal infections, reactivation of hepatitis B infection, lymphoma, heart failure, nervous system disorders, and allergic reactions are increased with treatment.
Serious adverse events associated with golimumab should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch/.
FDA approves radiotherapy for metastatic prostate cancer
Radium-223 dichloride, an alpha-particle–emitting radioactive agent, has been approved for treating men with castration-resistant prostate cancer that has spread to the bones, the Food and Drug Administration announced on May 15.
The agent "binds with minerals in the bone to deliver radiation directly to bone tumors," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, noted in the statement.
Ra-223 is the second drug for prostate cancer approved by the FDA in the last year that has been shown to extend the survival of men with metastatic prostate cancer, Dr. Pazdur noted. Enzalutamide (Xtandi), an androgen receptor inhibitor, was approved in August 2012 for treating men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel.
Approval of the radium-223 treatment, which will be marketed as Xofigo by Bayer Pharmaceuticals, was based on a phase III study of men with symptomatic castration-resistant prostate cancer with symptomatic bone metastases, and no other metastases, randomized to treatment with radium 233 (541 men) every 4 weeks for six cycles or placebo (268 men). All patients received best standard of care, which included external-beam radiation therapy, corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.
In an interim analysis, overall survival, the primary endpoint, was a median of 14 months among those in the radiotherapy arm, compared with 11.2 months among those on placebo, a highly statistically significant improvement, with a hazard ratio of 0.695. An updated exploratory analysis conducted later in the trial "confirmed Xofigo’s ability to extend overall survival," the FDA statement noted.
(The prescribing information states that in the updated analysis, median survival was 14.9 months vs. 11.3 months among those on placebo, with a hazard ratio of 0.695).
The most common side effects reported during clinical trials in men receiving the treatment, in 10% or more of patients, were nausea, diarrhea, vomiting and peripheral edema. The most common laboratory abnormalities detected, in 10% or more of patients, were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
Xofigo comes in a solution and is administered at 4-week intervals for six injection cycles; it is slowly administered intravenously over 1 minute. Safety and efficacy of more than six injections has not been studied, according to the prescribing information.
Radium-223 dichloride, an alpha-particle–emitting radioactive agent, has been approved for treating men with castration-resistant prostate cancer that has spread to the bones, the Food and Drug Administration announced on May 15.
The agent "binds with minerals in the bone to deliver radiation directly to bone tumors," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, noted in the statement.
Ra-223 is the second drug for prostate cancer approved by the FDA in the last year that has been shown to extend the survival of men with metastatic prostate cancer, Dr. Pazdur noted. Enzalutamide (Xtandi), an androgen receptor inhibitor, was approved in August 2012 for treating men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel.
Approval of the radium-223 treatment, which will be marketed as Xofigo by Bayer Pharmaceuticals, was based on a phase III study of men with symptomatic castration-resistant prostate cancer with symptomatic bone metastases, and no other metastases, randomized to treatment with radium 233 (541 men) every 4 weeks for six cycles or placebo (268 men). All patients received best standard of care, which included external-beam radiation therapy, corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.
In an interim analysis, overall survival, the primary endpoint, was a median of 14 months among those in the radiotherapy arm, compared with 11.2 months among those on placebo, a highly statistically significant improvement, with a hazard ratio of 0.695. An updated exploratory analysis conducted later in the trial "confirmed Xofigo’s ability to extend overall survival," the FDA statement noted.
(The prescribing information states that in the updated analysis, median survival was 14.9 months vs. 11.3 months among those on placebo, with a hazard ratio of 0.695).
The most common side effects reported during clinical trials in men receiving the treatment, in 10% or more of patients, were nausea, diarrhea, vomiting and peripheral edema. The most common laboratory abnormalities detected, in 10% or more of patients, were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
Xofigo comes in a solution and is administered at 4-week intervals for six injection cycles; it is slowly administered intravenously over 1 minute. Safety and efficacy of more than six injections has not been studied, according to the prescribing information.
Radium-223 dichloride, an alpha-particle–emitting radioactive agent, has been approved for treating men with castration-resistant prostate cancer that has spread to the bones, the Food and Drug Administration announced on May 15.
The agent "binds with minerals in the bone to deliver radiation directly to bone tumors," Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, noted in the statement.
Ra-223 is the second drug for prostate cancer approved by the FDA in the last year that has been shown to extend the survival of men with metastatic prostate cancer, Dr. Pazdur noted. Enzalutamide (Xtandi), an androgen receptor inhibitor, was approved in August 2012 for treating men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel.
Approval of the radium-223 treatment, which will be marketed as Xofigo by Bayer Pharmaceuticals, was based on a phase III study of men with symptomatic castration-resistant prostate cancer with symptomatic bone metastases, and no other metastases, randomized to treatment with radium 233 (541 men) every 4 weeks for six cycles or placebo (268 men). All patients received best standard of care, which included external-beam radiation therapy, corticosteroids, antiandrogens, estrogens, estramustine, or ketoconazole.
In an interim analysis, overall survival, the primary endpoint, was a median of 14 months among those in the radiotherapy arm, compared with 11.2 months among those on placebo, a highly statistically significant improvement, with a hazard ratio of 0.695. An updated exploratory analysis conducted later in the trial "confirmed Xofigo’s ability to extend overall survival," the FDA statement noted.
(The prescribing information states that in the updated analysis, median survival was 14.9 months vs. 11.3 months among those on placebo, with a hazard ratio of 0.695).
The most common side effects reported during clinical trials in men receiving the treatment, in 10% or more of patients, were nausea, diarrhea, vomiting and peripheral edema. The most common laboratory abnormalities detected, in 10% or more of patients, were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
Xofigo comes in a solution and is administered at 4-week intervals for six injection cycles; it is slowly administered intravenously over 1 minute. Safety and efficacy of more than six injections has not been studied, according to the prescribing information.
FDA approves oral nimodipine solution for enteral use only
An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.
The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.
The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.
The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.
The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."
The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.
The prescribing information is available here.
Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.
An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.
The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.
The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.
The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.
The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."
The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.
The prescribing information is available here.
Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.
An oral liquid formulation of nimodipine has been approved by the Food and Drug Administration to help reduce serious and fatal medication errors that have occurred when the drug is extracted for intravenous administration from the only previously approved formulation, a liquid-filled gel capsule, the agency announced on May 14.
The nimodipine oral solution was approved on May 10 for improving neurologic outcomes in adults who have had a subarachnoid hemorrhage. The liquid-filled gel capsule formulation was approved in 1988.
The new oral formulation, which will be marketed as Nymalize by Arbor Pharmaceuticals, can be administered orally or via a nasogastric or gastric tube, "and there is no need for a needle to be used, which is what caused past medication errors," Dr. Russell Katz, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in an FDA statement. "Having an oral version of this product may help reduce the medication errors we’ve seen from erroneous intravenous administration of the contents of oral capsules," he added.
The FDA has received reports of serious adverse events, including fatalities, associated with intravenous administration of the liquid contents of nimodipine capsules, including deaths, cardiac arrest, severe drops in blood pressure, and other cardiac complications. In 2006, a boxed warning was added to the prescribing information of nimodipine, a dihydropyridine calcium channel blocker, cautioning against intravenous use of the drug. And, in August 2010, the FDA issued a drug safety notice alerting health care professionals that nimodipine capsules should be administered only by mouth or through a feeding tube, and that it should "never" be administered intravenously.
The approved indication for liquid nimodipine is for the "improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I-V)."
The new formulation’s approval was based on clinical studies of nimodipine oral capsules in patients with subarachnoid hemorrhage. The prescribing information says that the bioavailability of nimodipine oral solution is comparable with that of nimodipine oral capsules, that hypotension is the most common adverse event in trials, and that blood pressure should be carefully monitored during treatment.
The prescribing information is available here.
Serious adverse events associated with Nymalize should be reported to the FDA’s MedWatch program or at 800-332-1088.
FDA approves once-daily combination drug for COPD
An inhaled powder formulation of the corticosteroid fluticasone furoate and vilanterol, a long-acting beta-2 agonist, has been approved for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema.
It has also been approved to reduce chronic obstructive pulmonary disease (COPD) exacerbations in patients with a history of exacerbations, according to a statement issued May 10 by the Food and Drug Administration. In studies of 7,700 patients diagnosed with COPD, those treated with the inhaled corticosteroid/long-acting beta-2 agonist (ICS/LABA) combination "showed improved lung function and reduced exacerbations compared to placebo," the statement said.
The fixed-dose combination of 100 mcg of fluticasone furoate with 25 mcg of vilanterol is formulated in a dry powder. It is administered once a day in a new inhaler that provides 30 doses, according to GlaxoSmithKline, which developed the product with Theravance. The product will be marketed as Breo Ellipta.
As with other LABAs, the prescribing information for this product includes a boxed warning about the risk of asthma-related deaths, although it is not approved for treating asthma. Nasopharyngitis, oral candidiasis, headache, and upper respiratory tract infections were among the most common side effects reported by patients using the product, according to the FDA.
The approval was announced less than a month after the majority of the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted to support approval of the product for long-term maintenance treatment of airflow obstruction and reducing COPD exacerbations. The panel nearly unanimously agreed that the treatment had "clinically meaningful" benefit as a long-term maintenance treatment for airflow obstruction They voted 8-5 that the data provided "substantial evidence" that reductions in exacerbations were clinically meaningful.
The two inhaled ICS/LABA treatments approved by the FDA for COPD are the combination of fluticasone propionate and salmeterol (Advair Diskus), also marketed by GSK, and the combination of budesonide and formoterol (Symbicort). Both are administered twice a day. Salmeterol and formoterol are both available as separate products to treat COPD. Vilanterol, which is the LABA component of Breo Ellipta, will not be available separately.
The label for Breo Ellipta can be found here.
An inhaled powder formulation of the corticosteroid fluticasone furoate and vilanterol, a long-acting beta-2 agonist, has been approved for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema.
It has also been approved to reduce chronic obstructive pulmonary disease (COPD) exacerbations in patients with a history of exacerbations, according to a statement issued May 10 by the Food and Drug Administration. In studies of 7,700 patients diagnosed with COPD, those treated with the inhaled corticosteroid/long-acting beta-2 agonist (ICS/LABA) combination "showed improved lung function and reduced exacerbations compared to placebo," the statement said.
The fixed-dose combination of 100 mcg of fluticasone furoate with 25 mcg of vilanterol is formulated in a dry powder. It is administered once a day in a new inhaler that provides 30 doses, according to GlaxoSmithKline, which developed the product with Theravance. The product will be marketed as Breo Ellipta.
As with other LABAs, the prescribing information for this product includes a boxed warning about the risk of asthma-related deaths, although it is not approved for treating asthma. Nasopharyngitis, oral candidiasis, headache, and upper respiratory tract infections were among the most common side effects reported by patients using the product, according to the FDA.
The approval was announced less than a month after the majority of the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted to support approval of the product for long-term maintenance treatment of airflow obstruction and reducing COPD exacerbations. The panel nearly unanimously agreed that the treatment had "clinically meaningful" benefit as a long-term maintenance treatment for airflow obstruction They voted 8-5 that the data provided "substantial evidence" that reductions in exacerbations were clinically meaningful.
The two inhaled ICS/LABA treatments approved by the FDA for COPD are the combination of fluticasone propionate and salmeterol (Advair Diskus), also marketed by GSK, and the combination of budesonide and formoterol (Symbicort). Both are administered twice a day. Salmeterol and formoterol are both available as separate products to treat COPD. Vilanterol, which is the LABA component of Breo Ellipta, will not be available separately.
The label for Breo Ellipta can be found here.
An inhaled powder formulation of the corticosteroid fluticasone furoate and vilanterol, a long-acting beta-2 agonist, has been approved for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease, including chronic bronchitis and/or emphysema.
It has also been approved to reduce chronic obstructive pulmonary disease (COPD) exacerbations in patients with a history of exacerbations, according to a statement issued May 10 by the Food and Drug Administration. In studies of 7,700 patients diagnosed with COPD, those treated with the inhaled corticosteroid/long-acting beta-2 agonist (ICS/LABA) combination "showed improved lung function and reduced exacerbations compared to placebo," the statement said.
The fixed-dose combination of 100 mcg of fluticasone furoate with 25 mcg of vilanterol is formulated in a dry powder. It is administered once a day in a new inhaler that provides 30 doses, according to GlaxoSmithKline, which developed the product with Theravance. The product will be marketed as Breo Ellipta.
As with other LABAs, the prescribing information for this product includes a boxed warning about the risk of asthma-related deaths, although it is not approved for treating asthma. Nasopharyngitis, oral candidiasis, headache, and upper respiratory tract infections were among the most common side effects reported by patients using the product, according to the FDA.
The approval was announced less than a month after the majority of the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted to support approval of the product for long-term maintenance treatment of airflow obstruction and reducing COPD exacerbations. The panel nearly unanimously agreed that the treatment had "clinically meaningful" benefit as a long-term maintenance treatment for airflow obstruction They voted 8-5 that the data provided "substantial evidence" that reductions in exacerbations were clinically meaningful.
The two inhaled ICS/LABA treatments approved by the FDA for COPD are the combination of fluticasone propionate and salmeterol (Advair Diskus), also marketed by GSK, and the combination of budesonide and formoterol (Symbicort). Both are administered twice a day. Salmeterol and formoterol are both available as separate products to treat COPD. Vilanterol, which is the LABA component of Breo Ellipta, will not be available separately.
The label for Breo Ellipta can be found here.
DEA scheduling brings weight-loss drug closer to market
Lorcaserin, a serotonin receptor agonist approved as a weight loss agent in 2012, has been scheduled as a schedule IV drug and is expected to be available within weeks, according to the manufacturer, Arena Pharmaceuticals.
The Drug Enforcement Administration (DEA) has placed lorcaserin (Belviq) in the schedule IV category of the Controlled Substances Act, which is for drugs with "a low potential for abuse and low risk of dependence." Other schedule IV drugs are alprazolam (Xanax), diazepam (Valium), and zolpidem (Ambien). Lorcaserin will be available 30 days after the final rule on the scheduling is published in the May 8th Federal Register, according to a May 7 statement issued by Arena.
The final rule in the Federal Register says that, on the basis of a review of the available data, the DEA determined that lorcaserin has a low potential for abuse relative to schedule III drugs, such as ketamine, and that the overall abuse potential of lorcaserin is comparable to schedule IV drugs, such a zolpidem. "Abuse of lorcaserin may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. This finding is based on the ability of lorcaserin to produce positive subjective effects at supratherapeutic doses," according to the final rule.
After two FDA advisory panel meetings, the FDA approved lorcaserin in June 2012 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of at least 30 kg/m2 (obese), or at least 27 kg/m2 (overweight) with at least one weight-related comorbid condition. The drug could not be marketed until the DEA finalized its decision regarding scheduling.
Because of concerns regarding the potential for valvulopathy associated with treatment, the company’s postmarketing commitments include conducting six studies, including a long-term cardiovascular outcomes trial. The prescribing information includes a recommendation to consider discontinuing treatment if patients develop signs to symptoms indicative of valvular heart disease and to evaluate patients for valvulopathy. Lorcaserin activates the serotonin 2C receptor, but at the approved dose of 10 mg twice a day, "does not appear to activate the serotonin 2B receptor," the FDA said in the June 27, 2012, approval announcement.
Weight-loss drugs fenfluramine and dexfenfluramine were taken off the market in 1997 after they were associated with valvular damage that was thought to be related to activation of the serotonin 2B receptor on cardiac tissue, according to the FDA.
Arena will be marketing lorcaserin as Belviq.
Lorcaserin, a serotonin receptor agonist approved as a weight loss agent in 2012, has been scheduled as a schedule IV drug and is expected to be available within weeks, according to the manufacturer, Arena Pharmaceuticals.
The Drug Enforcement Administration (DEA) has placed lorcaserin (Belviq) in the schedule IV category of the Controlled Substances Act, which is for drugs with "a low potential for abuse and low risk of dependence." Other schedule IV drugs are alprazolam (Xanax), diazepam (Valium), and zolpidem (Ambien). Lorcaserin will be available 30 days after the final rule on the scheduling is published in the May 8th Federal Register, according to a May 7 statement issued by Arena.
The final rule in the Federal Register says that, on the basis of a review of the available data, the DEA determined that lorcaserin has a low potential for abuse relative to schedule III drugs, such as ketamine, and that the overall abuse potential of lorcaserin is comparable to schedule IV drugs, such a zolpidem. "Abuse of lorcaserin may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. This finding is based on the ability of lorcaserin to produce positive subjective effects at supratherapeutic doses," according to the final rule.
After two FDA advisory panel meetings, the FDA approved lorcaserin in June 2012 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of at least 30 kg/m2 (obese), or at least 27 kg/m2 (overweight) with at least one weight-related comorbid condition. The drug could not be marketed until the DEA finalized its decision regarding scheduling.
Because of concerns regarding the potential for valvulopathy associated with treatment, the company’s postmarketing commitments include conducting six studies, including a long-term cardiovascular outcomes trial. The prescribing information includes a recommendation to consider discontinuing treatment if patients develop signs to symptoms indicative of valvular heart disease and to evaluate patients for valvulopathy. Lorcaserin activates the serotonin 2C receptor, but at the approved dose of 10 mg twice a day, "does not appear to activate the serotonin 2B receptor," the FDA said in the June 27, 2012, approval announcement.
Weight-loss drugs fenfluramine and dexfenfluramine were taken off the market in 1997 after they were associated with valvular damage that was thought to be related to activation of the serotonin 2B receptor on cardiac tissue, according to the FDA.
Arena will be marketing lorcaserin as Belviq.
Lorcaserin, a serotonin receptor agonist approved as a weight loss agent in 2012, has been scheduled as a schedule IV drug and is expected to be available within weeks, according to the manufacturer, Arena Pharmaceuticals.
The Drug Enforcement Administration (DEA) has placed lorcaserin (Belviq) in the schedule IV category of the Controlled Substances Act, which is for drugs with "a low potential for abuse and low risk of dependence." Other schedule IV drugs are alprazolam (Xanax), diazepam (Valium), and zolpidem (Ambien). Lorcaserin will be available 30 days after the final rule on the scheduling is published in the May 8th Federal Register, according to a May 7 statement issued by Arena.
The final rule in the Federal Register says that, on the basis of a review of the available data, the DEA determined that lorcaserin has a low potential for abuse relative to schedule III drugs, such as ketamine, and that the overall abuse potential of lorcaserin is comparable to schedule IV drugs, such a zolpidem. "Abuse of lorcaserin may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III. This finding is based on the ability of lorcaserin to produce positive subjective effects at supratherapeutic doses," according to the final rule.
After two FDA advisory panel meetings, the FDA approved lorcaserin in June 2012 as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of at least 30 kg/m2 (obese), or at least 27 kg/m2 (overweight) with at least one weight-related comorbid condition. The drug could not be marketed until the DEA finalized its decision regarding scheduling.
Because of concerns regarding the potential for valvulopathy associated with treatment, the company’s postmarketing commitments include conducting six studies, including a long-term cardiovascular outcomes trial. The prescribing information includes a recommendation to consider discontinuing treatment if patients develop signs to symptoms indicative of valvular heart disease and to evaluate patients for valvulopathy. Lorcaserin activates the serotonin 2C receptor, but at the approved dose of 10 mg twice a day, "does not appear to activate the serotonin 2B receptor," the FDA said in the June 27, 2012, approval announcement.
Weight-loss drugs fenfluramine and dexfenfluramine were taken off the market in 1997 after they were associated with valvular damage that was thought to be related to activation of the serotonin 2B receptor on cardiac tissue, according to the FDA.
Arena will be marketing lorcaserin as Belviq.