Elizabeth Mechcatie

The vaccine for the upcoming influenza season will contain the same three strains included in this past season's vaccine, the Food and Drug Administration announced.

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

“There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness,” according to the FDA statement.

“However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications,” according to the FDA statement.

Vaccines licensed for use in the United States include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement.

On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

The vaccine for the upcoming influenza season will contain the same three strains included in this past season's vaccine, the Food and Drug Administration announced.

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

“There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness,” according to the FDA statement.

“However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications,” according to the FDA statement.

Vaccines licensed for use in the United States include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement.

On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

The vaccine for the upcoming influenza season will contain the same three strains included in this past season's vaccine, the Food and Drug Administration announced.

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

“There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness,” according to the FDA statement.

“However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications,” according to the FDA statement.

Vaccines licensed for use in the United States include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement.

On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

A subcutaneous formulation of abatacept that patients can inject themselves has been approved by the Food and Drug Administration, according to a statement issued July 29 by the manufacturer, Bristol-Myers Squibb.

Like the intravenous formulation, this preparation is approved for treatment of adults with moderate to severe rheumatoid arthritis and can be used as monotherapy or in combination with disease-modifying antirheumatic drugs, other than tumor necrosis factor antagonists. Intravenous abatacept is also approved as a treatment for children aged 6 years and older who have moderately to severely active polyarticular juvenile idiopathic arthritis. The subcutaneous formulation has not been studied in pediatric patients, according to the Bristol-Myers Squibb statement.

The IV formulation of abatacept, a selective T-cell costimulator modulator marketed as Orencia, was approved in 2005.

The approved dosing of subcutaneous abatacept is a fixed 125 mg dose, administered once a week after a single IV loading dose of approximately 10 mg/kg. Patients who are not able to receive an infusion may start weekly subcutaneous injections of abatacept, without the IV loading dose. Those switching from IV abatacept to subcutaneous therapy should administer the first subcutaneous dose instead of the next IV dose, according to the revised prescribing information.

The efficacy of subcutaneous therapy was similar to IV therapy in the ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) study of almost 1,500 patients with moderately to severely active RA, most of whom had not had adequate responses to methotrexate alone, according to Bristol-Myers Squibb. The study, a phase III noninferiority study, compared treatment with subcutaneous abatacept plus methotrexate (after a single IV loading dose of about 10 mg/kg of abatacept) to IV abatacept plus methotrexate on days 1, 15, 29, and then every 4 weeks.

At 6 months, 76% of patients in both groups had achieved an ACR 20 response. ACR 50 and ACR 70 responses, as well as pain, physical, function, and global assessments for disease activity – and the safety profile –were also comparable between the two groups. Side effects included headache, nasopharyngitis, and upper respiratory tract infections; 2.6% of those who received the subcutaneous injections had injection-site reactions.

The rate of serious adverse events was 4.2% among those on subcutaneous (SC) abatacept and 4.9% of those in the IV group, and included serious infections (0.7% of those on subcutaneous dosing and 1.4% of those on the IV dose) and malignancies (under 1% in both groups).

Immunogenicity was seen in 1.1% of those on SC treatment and 2.3% of those on IV therapy, but this did not correlate with effects on pharmacokinetics, efficacy, or safety, the statement said.

The SC formulation will be marketed as Orencia SC and will be available in September, according to Bristol-Myers Squibb. The price is not yet available, a company spokesperson said.

A subcutaneous formulation of abatacept that patients can inject themselves has been approved by the Food and Drug Administration, according to a statement issued July 29 by the manufacturer, Bristol-Myers Squibb.

Like the intravenous formulation, this preparation is approved for treatment of adults with moderate to severe rheumatoid arthritis and can be used as monotherapy or in combination with disease-modifying antirheumatic drugs, other than tumor necrosis factor antagonists. Intravenous abatacept is also approved as a treatment for children aged 6 years and older who have moderately to severely active polyarticular juvenile idiopathic arthritis. The subcutaneous formulation has not been studied in pediatric patients, according to the Bristol-Myers Squibb statement.

The IV formulation of abatacept, a selective T-cell costimulator modulator marketed as Orencia, was approved in 2005.

The approved dosing of subcutaneous abatacept is a fixed 125 mg dose, administered once a week after a single IV loading dose of approximately 10 mg/kg. Patients who are not able to receive an infusion may start weekly subcutaneous injections of abatacept, without the IV loading dose. Those switching from IV abatacept to subcutaneous therapy should administer the first subcutaneous dose instead of the next IV dose, according to the revised prescribing information.

The efficacy of subcutaneous therapy was similar to IV therapy in the ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) study of almost 1,500 patients with moderately to severely active RA, most of whom had not had adequate responses to methotrexate alone, according to Bristol-Myers Squibb. The study, a phase III noninferiority study, compared treatment with subcutaneous abatacept plus methotrexate (after a single IV loading dose of about 10 mg/kg of abatacept) to IV abatacept plus methotrexate on days 1, 15, 29, and then every 4 weeks.

At 6 months, 76% of patients in both groups had achieved an ACR 20 response. ACR 50 and ACR 70 responses, as well as pain, physical, function, and global assessments for disease activity – and the safety profile –were also comparable between the two groups. Side effects included headache, nasopharyngitis, and upper respiratory tract infections; 2.6% of those who received the subcutaneous injections had injection-site reactions.

The rate of serious adverse events was 4.2% among those on subcutaneous (SC) abatacept and 4.9% of those in the IV group, and included serious infections (0.7% of those on subcutaneous dosing and 1.4% of those on the IV dose) and malignancies (under 1% in both groups).

Immunogenicity was seen in 1.1% of those on SC treatment and 2.3% of those on IV therapy, but this did not correlate with effects on pharmacokinetics, efficacy, or safety, the statement said.

The SC formulation will be marketed as Orencia SC and will be available in September, according to Bristol-Myers Squibb. The price is not yet available, a company spokesperson said.

A subcutaneous formulation of abatacept that patients can inject themselves has been approved by the Food and Drug Administration, according to a statement issued July 29 by the manufacturer, Bristol-Myers Squibb.

Like the intravenous formulation, this preparation is approved for treatment of adults with moderate to severe rheumatoid arthritis and can be used as monotherapy or in combination with disease-modifying antirheumatic drugs, other than tumor necrosis factor antagonists. Intravenous abatacept is also approved as a treatment for children aged 6 years and older who have moderately to severely active polyarticular juvenile idiopathic arthritis. The subcutaneous formulation has not been studied in pediatric patients, according to the Bristol-Myers Squibb statement.

The IV formulation of abatacept, a selective T-cell costimulator modulator marketed as Orencia, was approved in 2005.

The approved dosing of subcutaneous abatacept is a fixed 125 mg dose, administered once a week after a single IV loading dose of approximately 10 mg/kg. Patients who are not able to receive an infusion may start weekly subcutaneous injections of abatacept, without the IV loading dose. Those switching from IV abatacept to subcutaneous therapy should administer the first subcutaneous dose instead of the next IV dose, according to the revised prescribing information.

The efficacy of subcutaneous therapy was similar to IV therapy in the ACQUIRE (Abatacept Comparison of Sub(Qu)cutaneous vs. Intravenous in Inadequate Responders to Methotrexate) study of almost 1,500 patients with moderately to severely active RA, most of whom had not had adequate responses to methotrexate alone, according to Bristol-Myers Squibb. The study, a phase III noninferiority study, compared treatment with subcutaneous abatacept plus methotrexate (after a single IV loading dose of about 10 mg/kg of abatacept) to IV abatacept plus methotrexate on days 1, 15, 29, and then every 4 weeks.

At 6 months, 76% of patients in both groups had achieved an ACR 20 response. ACR 50 and ACR 70 responses, as well as pain, physical, function, and global assessments for disease activity – and the safety profile –were also comparable between the two groups. Side effects included headache, nasopharyngitis, and upper respiratory tract infections; 2.6% of those who received the subcutaneous injections had injection-site reactions.

The rate of serious adverse events was 4.2% among those on subcutaneous (SC) abatacept and 4.9% of those in the IV group, and included serious infections (0.7% of those on subcutaneous dosing and 1.4% of those on the IV dose) and malignancies (under 1% in both groups).

Immunogenicity was seen in 1.1% of those on SC treatment and 2.3% of those on IV therapy, but this did not correlate with effects on pharmacokinetics, efficacy, or safety, the statement said.

The SC formulation will be marketed as Orencia SC and will be available in September, according to Bristol-Myers Squibb. The price is not yet available, a company spokesperson said.

The risk of stroke is significantly elevated among traumatic brain injury patients in the first 5 years after injury, particularly during the first 3 months and if it involved a skull fracture, Taiwanese researchers reported July 28 in Stroke.

"To the best of our knowledge, this is the first study to demonstrate that TBI [traumatic brain injury] is a potential risk factor for subsequent stroke," wrote Yi-Hua Chen, Ph.D., and her coauthors from Taipei (Taiwan) Medical University.

Noting that other studies have identified neurological disorders, epilepsy, psychiatric diseases, and other morbidities that occur during the years after a TBI, the authors wrote that this study "leads the way in identifying stroke as an additional neurological problem that may arise following TBI."

Because of the large number of people who have TBI and stroke, the study results have important clinical implications in managing patients with TBI, including "more intensive medical monitoring, support, and intervention" after a TBI – particularly during the first few months or years – and the need to educate families about the early signs and symptoms of stroke in patients who have had a TBI.

Medical professionals "should also be aware of the need to provide early neuroimaging examination ... for suspected stroke patients, particularly those with a history of TBI," Dr. Chen and her colleagues added.

Using records from a health insurance database, they identified about 23,000 adults who had received ambulatory or inpatient care for a diagnosis of TBI between 2001 and 2003 and almost 70,000 patients who did not have a TBI. They matched patients from the groups for sex, age, and year they received the index use of health care. The patients were followed for 5 years. Overall, their mean age was almost 42 years and a little over half were men. People who had had a stroke diagnosis previously were excluded (Stroke 2011 July 28 [doi:10.1161/STROKEAHA.111.620112]).

Stroke rates were significantly higher among those who had had a TBI across the three different time periods that the investigators evaluated. During the first 3 months, strokes occurred more often in TBI patients than among individuals in the comparison group (2.91% vs. 0.30%, respectively). Over 1 year, 4.17% of those with a TBI had a stroke, compared with 0.96% of control group patients. In a 5-year period, 8.20% of those with a TBI had a stroke vs. 3.89% of those in the comparison group.

After adjusting for certain comorbidities, regions of residence, and sociodemographic features, the risk of a stroke after a TBI was about tenfold greater over the first 3 months, almost 5 times greater over 1 year, and about two times greater over the 5-year follow-up.

The authors also found that the stroke risk was "more pronounced" among those who had a fractured skull, compared with the control group overall: The risk of stroke was almost 20-fold greater over 3 months, about 8 times greater over 1 year, and about three and a half times greater over 5 years. Those with a TBI were at a greater risk of having all subtypes of a stroke during the 5-year follow-up period.

They described the possible mechanism behind the increased risk of stroke after a TBI as "vague" and pointed out that more studies were needed to determine the mechanism. But they speculated about several possibilities, including damage to the cerebrovascular system disturbing the blood supply to the brain, leakage of blood caused partly by bleeding from an artery, as well as increased intracranial pressure and blood pressure that occur after TBI.

The authors had no disclosures.

The risk of stroke is significantly elevated among traumatic brain injury patients in the first 5 years after injury, particularly during the first 3 months and if it involved a skull fracture, Taiwanese researchers reported July 28 in Stroke.

"To the best of our knowledge, this is the first study to demonstrate that TBI [traumatic brain injury] is a potential risk factor for subsequent stroke," wrote Yi-Hua Chen, Ph.D., and her coauthors from Taipei (Taiwan) Medical University.

Noting that other studies have identified neurological disorders, epilepsy, psychiatric diseases, and other morbidities that occur during the years after a TBI, the authors wrote that this study "leads the way in identifying stroke as an additional neurological problem that may arise following TBI."

Because of the large number of people who have TBI and stroke, the study results have important clinical implications in managing patients with TBI, including "more intensive medical monitoring, support, and intervention" after a TBI – particularly during the first few months or years – and the need to educate families about the early signs and symptoms of stroke in patients who have had a TBI.

Medical professionals "should also be aware of the need to provide early neuroimaging examination ... for suspected stroke patients, particularly those with a history of TBI," Dr. Chen and her colleagues added.

Using records from a health insurance database, they identified about 23,000 adults who had received ambulatory or inpatient care for a diagnosis of TBI between 2001 and 2003 and almost 70,000 patients who did not have a TBI. They matched patients from the groups for sex, age, and year they received the index use of health care. The patients were followed for 5 years. Overall, their mean age was almost 42 years and a little over half were men. People who had had a stroke diagnosis previously were excluded (Stroke 2011 July 28 [doi:10.1161/STROKEAHA.111.620112]).

Stroke rates were significantly higher among those who had had a TBI across the three different time periods that the investigators evaluated. During the first 3 months, strokes occurred more often in TBI patients than among individuals in the comparison group (2.91% vs. 0.30%, respectively). Over 1 year, 4.17% of those with a TBI had a stroke, compared with 0.96% of control group patients. In a 5-year period, 8.20% of those with a TBI had a stroke vs. 3.89% of those in the comparison group.

After adjusting for certain comorbidities, regions of residence, and sociodemographic features, the risk of a stroke after a TBI was about tenfold greater over the first 3 months, almost 5 times greater over 1 year, and about two times greater over the 5-year follow-up.

The authors also found that the stroke risk was "more pronounced" among those who had a fractured skull, compared with the control group overall: The risk of stroke was almost 20-fold greater over 3 months, about 8 times greater over 1 year, and about three and a half times greater over 5 years. Those with a TBI were at a greater risk of having all subtypes of a stroke during the 5-year follow-up period.

They described the possible mechanism behind the increased risk of stroke after a TBI as "vague" and pointed out that more studies were needed to determine the mechanism. But they speculated about several possibilities, including damage to the cerebrovascular system disturbing the blood supply to the brain, leakage of blood caused partly by bleeding from an artery, as well as increased intracranial pressure and blood pressure that occur after TBI.

The authors had no disclosures.

The risk of stroke is significantly elevated among traumatic brain injury patients in the first 5 years after injury, particularly during the first 3 months and if it involved a skull fracture, Taiwanese researchers reported July 28 in Stroke.

"To the best of our knowledge, this is the first study to demonstrate that TBI [traumatic brain injury] is a potential risk factor for subsequent stroke," wrote Yi-Hua Chen, Ph.D., and her coauthors from Taipei (Taiwan) Medical University.

Noting that other studies have identified neurological disorders, epilepsy, psychiatric diseases, and other morbidities that occur during the years after a TBI, the authors wrote that this study "leads the way in identifying stroke as an additional neurological problem that may arise following TBI."

Because of the large number of people who have TBI and stroke, the study results have important clinical implications in managing patients with TBI, including "more intensive medical monitoring, support, and intervention" after a TBI – particularly during the first few months or years – and the need to educate families about the early signs and symptoms of stroke in patients who have had a TBI.

Medical professionals "should also be aware of the need to provide early neuroimaging examination ... for suspected stroke patients, particularly those with a history of TBI," Dr. Chen and her colleagues added.

Using records from a health insurance database, they identified about 23,000 adults who had received ambulatory or inpatient care for a diagnosis of TBI between 2001 and 2003 and almost 70,000 patients who did not have a TBI. They matched patients from the groups for sex, age, and year they received the index use of health care. The patients were followed for 5 years. Overall, their mean age was almost 42 years and a little over half were men. People who had had a stroke diagnosis previously were excluded (Stroke 2011 July 28 [doi:10.1161/STROKEAHA.111.620112]).

Stroke rates were significantly higher among those who had had a TBI across the three different time periods that the investigators evaluated. During the first 3 months, strokes occurred more often in TBI patients than among individuals in the comparison group (2.91% vs. 0.30%, respectively). Over 1 year, 4.17% of those with a TBI had a stroke, compared with 0.96% of control group patients. In a 5-year period, 8.20% of those with a TBI had a stroke vs. 3.89% of those in the comparison group.

After adjusting for certain comorbidities, regions of residence, and sociodemographic features, the risk of a stroke after a TBI was about tenfold greater over the first 3 months, almost 5 times greater over 1 year, and about two times greater over the 5-year follow-up.

The authors also found that the stroke risk was "more pronounced" among those who had a fractured skull, compared with the control group overall: The risk of stroke was almost 20-fold greater over 3 months, about 8 times greater over 1 year, and about three and a half times greater over 5 years. Those with a TBI were at a greater risk of having all subtypes of a stroke during the 5-year follow-up period.

They described the possible mechanism behind the increased risk of stroke after a TBI as "vague" and pointed out that more studies were needed to determine the mechanism. But they speculated about several possibilities, including damage to the cerebrovascular system disturbing the blood supply to the brain, leakage of blood caused partly by bleeding from an artery, as well as increased intracranial pressure and blood pressure that occur after TBI.

The authors had no disclosures.

The antibacterial drug linezolid and methylene blue can interact with serotoninergic psychiatric drugs, resulting in serious central nervous system reactions, the Food and Drug Administration announced July 26 in two separate but similarly worded safety advisories.

Cases of serotonin syndrome associated with concomitant administration of linezolid and serotoninergic psychiatric medications, including some deaths, have been reported to the FDA’s adverse event reporting system (AERS), according to one of the statements. More cases were identified in a literature search, including at least one fatal case (Pharmacotherapy 2006;26:269-76).

Serious CNS reactions have also been reported to AERS in patients treated with methylene blue and serotonergic psychiatric medications, and more cases have also been reported in the literature, according to the second advisory, which does not mention any reports of fatal cases. These events have included reports of lethargy, confusion, delirium, and coma – often with neurologic symptoms, such as myoclonus, expressive aphasia, seizures, or autonomic symptoms.

The exact mechanism of action behind these interactions is unknown, the FDA statement says, but adds that both agents are known reversible monoamine oxidase inhibitors and when either is administered along with a serotonergic medication, high levels of serotonin can build up in the brain resulting in serotonin syndrome, which is characterized by symptoms that include mental changes.

The statements advise that linezolid or methylene blue should "generally not be given" to patients on serotonergic drugs. However, the FDA adds that "there are some conditions that may be life threatening or require urgent treatment" with either agent.

In the case of linezolid, those situations include when linezolid is needed to treat vancomycin-resistant Enterococcus faecium (VRE) or other types of infections such as nosocomial pneumonia or complicated skin and skin structure infections, including those cases caused by methicillin-resistant Staphylococcus aureus. For methylene blue, those cases include methemoglobinemia, cyanide poisoning, or ifosfamide-induced encephalopathy.

The advisories include a complete list of psychiatric drugs with serotonergic activity, including selective serotonin reuptake inhibitors and tricyclic antidepressants.

Serious adverse reactions resulting from concomitant use of linezolid or methylene blue and serotonergic drugs should be reported to the FDA’s MedWatch program or at 800-332-1088.

The antibacterial drug linezolid and methylene blue can interact with serotoninergic psychiatric drugs, resulting in serious central nervous system reactions, the Food and Drug Administration announced July 26 in two separate but similarly worded safety advisories.

Cases of serotonin syndrome associated with concomitant administration of linezolid and serotoninergic psychiatric medications, including some deaths, have been reported to the FDA’s adverse event reporting system (AERS), according to one of the statements. More cases were identified in a literature search, including at least one fatal case (Pharmacotherapy 2006;26:269-76).

Serious CNS reactions have also been reported to AERS in patients treated with methylene blue and serotonergic psychiatric medications, and more cases have also been reported in the literature, according to the second advisory, which does not mention any reports of fatal cases. These events have included reports of lethargy, confusion, delirium, and coma – often with neurologic symptoms, such as myoclonus, expressive aphasia, seizures, or autonomic symptoms.

The exact mechanism of action behind these interactions is unknown, the FDA statement says, but adds that both agents are known reversible monoamine oxidase inhibitors and when either is administered along with a serotonergic medication, high levels of serotonin can build up in the brain resulting in serotonin syndrome, which is characterized by symptoms that include mental changes.

The statements advise that linezolid or methylene blue should "generally not be given" to patients on serotonergic drugs. However, the FDA adds that "there are some conditions that may be life threatening or require urgent treatment" with either agent.

In the case of linezolid, those situations include when linezolid is needed to treat vancomycin-resistant Enterococcus faecium (VRE) or other types of infections such as nosocomial pneumonia or complicated skin and skin structure infections, including those cases caused by methicillin-resistant Staphylococcus aureus. For methylene blue, those cases include methemoglobinemia, cyanide poisoning, or ifosfamide-induced encephalopathy.

The advisories include a complete list of psychiatric drugs with serotonergic activity, including selective serotonin reuptake inhibitors and tricyclic antidepressants.

Serious adverse reactions resulting from concomitant use of linezolid or methylene blue and serotonergic drugs should be reported to the FDA’s MedWatch program or at 800-332-1088.

The antibacterial drug linezolid and methylene blue can interact with serotoninergic psychiatric drugs, resulting in serious central nervous system reactions, the Food and Drug Administration announced July 26 in two separate but similarly worded safety advisories.

Cases of serotonin syndrome associated with concomitant administration of linezolid and serotoninergic psychiatric medications, including some deaths, have been reported to the FDA’s adverse event reporting system (AERS), according to one of the statements. More cases were identified in a literature search, including at least one fatal case (Pharmacotherapy 2006;26:269-76).

Serious CNS reactions have also been reported to AERS in patients treated with methylene blue and serotonergic psychiatric medications, and more cases have also been reported in the literature, according to the second advisory, which does not mention any reports of fatal cases. These events have included reports of lethargy, confusion, delirium, and coma – often with neurologic symptoms, such as myoclonus, expressive aphasia, seizures, or autonomic symptoms.

The exact mechanism of action behind these interactions is unknown, the FDA statement says, but adds that both agents are known reversible monoamine oxidase inhibitors and when either is administered along with a serotonergic medication, high levels of serotonin can build up in the brain resulting in serotonin syndrome, which is characterized by symptoms that include mental changes.

The statements advise that linezolid or methylene blue should "generally not be given" to patients on serotonergic drugs. However, the FDA adds that "there are some conditions that may be life threatening or require urgent treatment" with either agent.

In the case of linezolid, those situations include when linezolid is needed to treat vancomycin-resistant Enterococcus faecium (VRE) or other types of infections such as nosocomial pneumonia or complicated skin and skin structure infections, including those cases caused by methicillin-resistant Staphylococcus aureus. For methylene blue, those cases include methemoglobinemia, cyanide poisoning, or ifosfamide-induced encephalopathy.

The advisories include a complete list of psychiatric drugs with serotonergic activity, including selective serotonin reuptake inhibitors and tricyclic antidepressants.

Serious adverse reactions resulting from concomitant use of linezolid or methylene blue and serotonergic drugs should be reported to the FDA’s MedWatch program or at 800-332-1088.

An updated label for the smoking cessation drug varenicline that includes new safety data involving people with cardiovascular disease has been approved by the Food and Drug Administration, the agency has announced.

Also added to the label is information on the use of varenicline in patients with chronic obstructive pulmonary disease (COPD) and alternative directions for selecting a date to quit smoking, according to the July 22 announcement. Varenicline, a nicotinic receptor partial agonist, was approved in 2006 for use as an aid to smoking cessation treatment; it is marketed by Pfizer as Chantix.

©Photosani/Fotolia.com

The cardiovascular safety information summarizes the results of a randomized study of 700 smokers with stable cardiovascular disease who received 1 mg of varenicline twice a day or placebo for 12 weeks and who were followed for an additional 40 weeks. The study found that those on varenicline had twice the chance of staying abstinent from smoking for as long as 12 months, compared to those on placebo. But it also found that treatment "may be associated with a small increased risk of certain cardiovascular adverse events in these patients."

Health care professionals are advised to "always weigh the potential benefits of Chantix against its potential risks when deciding to use the drug in patients with cardiovascular disease."

In a safety alert issued by the FDA, the agency stated that over 52 weeks, there were more reports of certain cardiovascular events among those on varenicline compared with those on placebo. Those events included nonfatal myocardial infarction (2% vs. 0.9%) and the need for coronary vascularization (2.3% vs. 0.9%).

The information on patients with COPD summarizes the results of a 52-week study of 460 patients, aged 35 years and older with mild to moderate COPD, that found that treatment with varenicline, 1 mg twice daily for 12 weeks, was more effective in helping these patients quit smoking and stay abstinent for as long as one year, when compared to placebo.

The varenicline label has advised that patients select a date to quit smoking and start taking varenicline 7 days before that date. The label still includes that recommendation, but now states that as an alternative, patients can start taking varenicline "and then quit smoking between days 8 and 35 of treatment."

That recommendation is based on the results of a randomized study of otherwise healthy smokers that found the alternative dosing schedule was more effective than placebo in helping patients quit smoking and remain abstinent for as long as 24 weeks. No new safety issues were identified in the study and adverse events were similar to those in the clinical trial described on the original drug label.

The Cardiovascular Risks of Varenicline

Earlier in July, the potential cardiovascular risks associated with varenicline received widespread media coverage with the online publication of a meta-analysis of 14 studies comparing the drug to placebo (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110218]).

The studies enrolled more than 8,000 patients, including almost 5,000 on varenicline (most were taking the 1 mg twice a day dose), treated from 7 to 52 weeks. Patients with cardiovascular disease were included in the trials, however all but one excluded those with unstable cardiovascular disease. The rate of serious cardiovascular events was significantly higher among those on varenicline compared with placebo (1.06% vs. 0.82%), which represented a 72% increased risk.

While the study had some limitations, it did raise safety concerns" about the potential for these events in people treated with the drug and follow-up safety studies should be conducted, the authors concluded.

In an accompanying editorial, Dr. J. Taylor Hays, of the Mayo Clinic, Rochester, Minn., wrote that "although their results suggest that a measure of caution should be taken in prescribing varenicline for the treatment of tobacco dependence, the small absolute risk of cardiovascular events associated with taking varenicline is outweighed by the enormous benefit of reducing cardiovascular morbidity and mortality that can be achieved with successful abstinence from smoking" (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110804]).

Dr. Hays has received grant funding from Pfizer to conduct a varenicline study. The lead author of the meta-analysis, Dr. Sonal Singh, of Johns Hopkins University, Baltimore, was supported with a grant from the National Center for Research Resources, a component of the National Institutes of Health. A coauthor, Dr. Curt Furberg, of Wake Forest University, Winston-Salem, N.C., who supervised the study, has been paid by plaintiffs for expert testimony on Pfizer’s COX-2 inhibitors.

A July 4 statement issued by Pfizer said that the company is discussing with the FDA a protocol for a meta-analysis of Pfizer’s clinical trial data to evaluate the drug’s cardiovascular risk. It also says that the company stands by the risk-benefit profile of varenicline and expressed concerns about the reliability of the meta-analysis, which includes the way cardiovascular events were counted and the small number of events that were the basis of the conclusions.

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

An updated label for the smoking cessation drug varenicline that includes new safety data involving people with cardiovascular disease has been approved by the Food and Drug Administration, the agency has announced.

Also added to the label is information on the use of varenicline in patients with chronic obstructive pulmonary disease (COPD) and alternative directions for selecting a date to quit smoking, according to the July 22 announcement. Varenicline, a nicotinic receptor partial agonist, was approved in 2006 for use as an aid to smoking cessation treatment; it is marketed by Pfizer as Chantix.

©Photosani/Fotolia.com

The cardiovascular safety information summarizes the results of a randomized study of 700 smokers with stable cardiovascular disease who received 1 mg of varenicline twice a day or placebo for 12 weeks and who were followed for an additional 40 weeks. The study found that those on varenicline had twice the chance of staying abstinent from smoking for as long as 12 months, compared to those on placebo. But it also found that treatment "may be associated with a small increased risk of certain cardiovascular adverse events in these patients."

Health care professionals are advised to "always weigh the potential benefits of Chantix against its potential risks when deciding to use the drug in patients with cardiovascular disease."

In a safety alert issued by the FDA, the agency stated that over 52 weeks, there were more reports of certain cardiovascular events among those on varenicline compared with those on placebo. Those events included nonfatal myocardial infarction (2% vs. 0.9%) and the need for coronary vascularization (2.3% vs. 0.9%).

The information on patients with COPD summarizes the results of a 52-week study of 460 patients, aged 35 years and older with mild to moderate COPD, that found that treatment with varenicline, 1 mg twice daily for 12 weeks, was more effective in helping these patients quit smoking and stay abstinent for as long as one year, when compared to placebo.

The varenicline label has advised that patients select a date to quit smoking and start taking varenicline 7 days before that date. The label still includes that recommendation, but now states that as an alternative, patients can start taking varenicline "and then quit smoking between days 8 and 35 of treatment."

That recommendation is based on the results of a randomized study of otherwise healthy smokers that found the alternative dosing schedule was more effective than placebo in helping patients quit smoking and remain abstinent for as long as 24 weeks. No new safety issues were identified in the study and adverse events were similar to those in the clinical trial described on the original drug label.

The Cardiovascular Risks of Varenicline

Earlier in July, the potential cardiovascular risks associated with varenicline received widespread media coverage with the online publication of a meta-analysis of 14 studies comparing the drug to placebo (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110218]).

The studies enrolled more than 8,000 patients, including almost 5,000 on varenicline (most were taking the 1 mg twice a day dose), treated from 7 to 52 weeks. Patients with cardiovascular disease were included in the trials, however all but one excluded those with unstable cardiovascular disease. The rate of serious cardiovascular events was significantly higher among those on varenicline compared with placebo (1.06% vs. 0.82%), which represented a 72% increased risk.

While the study had some limitations, it did raise safety concerns" about the potential for these events in people treated with the drug and follow-up safety studies should be conducted, the authors concluded.

In an accompanying editorial, Dr. J. Taylor Hays, of the Mayo Clinic, Rochester, Minn., wrote that "although their results suggest that a measure of caution should be taken in prescribing varenicline for the treatment of tobacco dependence, the small absolute risk of cardiovascular events associated with taking varenicline is outweighed by the enormous benefit of reducing cardiovascular morbidity and mortality that can be achieved with successful abstinence from smoking" (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110804]).

Dr. Hays has received grant funding from Pfizer to conduct a varenicline study. The lead author of the meta-analysis, Dr. Sonal Singh, of Johns Hopkins University, Baltimore, was supported with a grant from the National Center for Research Resources, a component of the National Institutes of Health. A coauthor, Dr. Curt Furberg, of Wake Forest University, Winston-Salem, N.C., who supervised the study, has been paid by plaintiffs for expert testimony on Pfizer’s COX-2 inhibitors.

A July 4 statement issued by Pfizer said that the company is discussing with the FDA a protocol for a meta-analysis of Pfizer’s clinical trial data to evaluate the drug’s cardiovascular risk. It also says that the company stands by the risk-benefit profile of varenicline and expressed concerns about the reliability of the meta-analysis, which includes the way cardiovascular events were counted and the small number of events that were the basis of the conclusions.

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

An updated label for the smoking cessation drug varenicline that includes new safety data involving people with cardiovascular disease has been approved by the Food and Drug Administration, the agency has announced.

Also added to the label is information on the use of varenicline in patients with chronic obstructive pulmonary disease (COPD) and alternative directions for selecting a date to quit smoking, according to the July 22 announcement. Varenicline, a nicotinic receptor partial agonist, was approved in 2006 for use as an aid to smoking cessation treatment; it is marketed by Pfizer as Chantix.

©Photosani/Fotolia.com

The cardiovascular safety information summarizes the results of a randomized study of 700 smokers with stable cardiovascular disease who received 1 mg of varenicline twice a day or placebo for 12 weeks and who were followed for an additional 40 weeks. The study found that those on varenicline had twice the chance of staying abstinent from smoking for as long as 12 months, compared to those on placebo. But it also found that treatment "may be associated with a small increased risk of certain cardiovascular adverse events in these patients."

Health care professionals are advised to "always weigh the potential benefits of Chantix against its potential risks when deciding to use the drug in patients with cardiovascular disease."

In a safety alert issued by the FDA, the agency stated that over 52 weeks, there were more reports of certain cardiovascular events among those on varenicline compared with those on placebo. Those events included nonfatal myocardial infarction (2% vs. 0.9%) and the need for coronary vascularization (2.3% vs. 0.9%).

The information on patients with COPD summarizes the results of a 52-week study of 460 patients, aged 35 years and older with mild to moderate COPD, that found that treatment with varenicline, 1 mg twice daily for 12 weeks, was more effective in helping these patients quit smoking and stay abstinent for as long as one year, when compared to placebo.

The varenicline label has advised that patients select a date to quit smoking and start taking varenicline 7 days before that date. The label still includes that recommendation, but now states that as an alternative, patients can start taking varenicline "and then quit smoking between days 8 and 35 of treatment."

That recommendation is based on the results of a randomized study of otherwise healthy smokers that found the alternative dosing schedule was more effective than placebo in helping patients quit smoking and remain abstinent for as long as 24 weeks. No new safety issues were identified in the study and adverse events were similar to those in the clinical trial described on the original drug label.

The Cardiovascular Risks of Varenicline

Earlier in July, the potential cardiovascular risks associated with varenicline received widespread media coverage with the online publication of a meta-analysis of 14 studies comparing the drug to placebo (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110218]).

The studies enrolled more than 8,000 patients, including almost 5,000 on varenicline (most were taking the 1 mg twice a day dose), treated from 7 to 52 weeks. Patients with cardiovascular disease were included in the trials, however all but one excluded those with unstable cardiovascular disease. The rate of serious cardiovascular events was significantly higher among those on varenicline compared with placebo (1.06% vs. 0.82%), which represented a 72% increased risk.

While the study had some limitations, it did raise safety concerns" about the potential for these events in people treated with the drug and follow-up safety studies should be conducted, the authors concluded.

In an accompanying editorial, Dr. J. Taylor Hays, of the Mayo Clinic, Rochester, Minn., wrote that "although their results suggest that a measure of caution should be taken in prescribing varenicline for the treatment of tobacco dependence, the small absolute risk of cardiovascular events associated with taking varenicline is outweighed by the enormous benefit of reducing cardiovascular morbidity and mortality that can be achieved with successful abstinence from smoking" (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110804]).

Dr. Hays has received grant funding from Pfizer to conduct a varenicline study. The lead author of the meta-analysis, Dr. Sonal Singh, of Johns Hopkins University, Baltimore, was supported with a grant from the National Center for Research Resources, a component of the National Institutes of Health. A coauthor, Dr. Curt Furberg, of Wake Forest University, Winston-Salem, N.C., who supervised the study, has been paid by plaintiffs for expert testimony on Pfizer’s COX-2 inhibitors.

A July 4 statement issued by Pfizer said that the company is discussing with the FDA a protocol for a meta-analysis of Pfizer’s clinical trial data to evaluate the drug’s cardiovascular risk. It also says that the company stands by the risk-benefit profile of varenicline and expressed concerns about the reliability of the meta-analysis, which includes the way cardiovascular events were counted and the small number of events that were the basis of the conclusions.

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

SILVER SPRING, MD – A Food and Drug Administration advisory panel has backed the approval of infliximab to treat ulcerative colitis in children and adolescents.

The FDA’s Gastrointestinal Drugs Advisory Committee unanimously voted July 21 that the risk-benefit profile of infliximab supported this indication. The panel based its vote on results of an open label pediatric study and extrapolation of efficacy data in adult studies to pediatric patients.

All but one panelist voted that safety concerns remained that still had not been adequately addressed, particularly with longterm treatment. Panelists were most concerned about the unclear risk of immunogenicity associated with treatment and the risk of malignancies, notably, a safety signal for hepatosplenic T-cell lymphoma (HSTCL).

Infliximab, a tumor necrosis factor blocker marketed as Remicade by Centocor Ortho Biotech, was previously approved by the FDA for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

The manufacturer had proposed that this indication be expanded to include pediatric patients, citing an open label, single arm, 54-week study of 60 pediatric patients (median age 14.5 years) with moderate to severe ulcerative colitis, and two adult studies. In the pediatric study, 73% (44 patients) at week 8 had a clinical response to infliximab, given at a dose of 5 mg/kg intravenously at weeks 0, 2 and 6. Responders were then randomized to one of two maintenance doses.

Over an average of 38 weeks of follow-up, 23% of the patients had serious adverse events, including infection (12%), anemia (1.7%), and neutropenia (1.7%). There were no cases of tuberculosis or malignancies, which have been reported in children treated with TNF-blockers.

HSTCL has been reported in people treated with infliximab who also have been treated or were currently undergoing treatment with a thiopurine (azathioprine and mercaptopurine), according to the manufacturer.

As of April 2008, 48 malignancies in children and adolescents treated with infliximab or other TNF antagonists have been reported to the FDA’s adverse event reporting system, of which 25 were in pediatric patients with Crohn’s disease (21) or ulcerative colitis (4). Among these 25 cases were 10 reports of HSTCL. There are no known cases of HSTCL in patients treated with a TNF antagonist without a history of previous or concomitant thiopurine treatment, according to the FDA.

Panelists stressed the importance of following patients closely for malignancies and other risks associated with infliximab treatment and informing patients and their parents about the possible serious risks of treatment.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver. At this meeting two panelists were granted a waiver because of their expertise and the "paucity" of physicians on the committee with knowledge of the subject, according to the disclosure forms posted by the FDA before the meeting.

SILVER SPRING, MD – A Food and Drug Administration advisory panel has backed the approval of infliximab to treat ulcerative colitis in children and adolescents.

The FDA’s Gastrointestinal Drugs Advisory Committee unanimously voted July 21 that the risk-benefit profile of infliximab supported this indication. The panel based its vote on results of an open label pediatric study and extrapolation of efficacy data in adult studies to pediatric patients.

All but one panelist voted that safety concerns remained that still had not been adequately addressed, particularly with longterm treatment. Panelists were most concerned about the unclear risk of immunogenicity associated with treatment and the risk of malignancies, notably, a safety signal for hepatosplenic T-cell lymphoma (HSTCL).

Infliximab, a tumor necrosis factor blocker marketed as Remicade by Centocor Ortho Biotech, was previously approved by the FDA for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

The manufacturer had proposed that this indication be expanded to include pediatric patients, citing an open label, single arm, 54-week study of 60 pediatric patients (median age 14.5 years) with moderate to severe ulcerative colitis, and two adult studies. In the pediatric study, 73% (44 patients) at week 8 had a clinical response to infliximab, given at a dose of 5 mg/kg intravenously at weeks 0, 2 and 6. Responders were then randomized to one of two maintenance doses.

Over an average of 38 weeks of follow-up, 23% of the patients had serious adverse events, including infection (12%), anemia (1.7%), and neutropenia (1.7%). There were no cases of tuberculosis or malignancies, which have been reported in children treated with TNF-blockers.

HSTCL has been reported in people treated with infliximab who also have been treated or were currently undergoing treatment with a thiopurine (azathioprine and mercaptopurine), according to the manufacturer.

As of April 2008, 48 malignancies in children and adolescents treated with infliximab or other TNF antagonists have been reported to the FDA’s adverse event reporting system, of which 25 were in pediatric patients with Crohn’s disease (21) or ulcerative colitis (4). Among these 25 cases were 10 reports of HSTCL. There are no known cases of HSTCL in patients treated with a TNF antagonist without a history of previous or concomitant thiopurine treatment, according to the FDA.

Panelists stressed the importance of following patients closely for malignancies and other risks associated with infliximab treatment and informing patients and their parents about the possible serious risks of treatment.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver. At this meeting two panelists were granted a waiver because of their expertise and the "paucity" of physicians on the committee with knowledge of the subject, according to the disclosure forms posted by the FDA before the meeting.

SILVER SPRING, MD – A Food and Drug Administration advisory panel has backed the approval of infliximab to treat ulcerative colitis in children and adolescents.

The FDA’s Gastrointestinal Drugs Advisory Committee unanimously voted July 21 that the risk-benefit profile of infliximab supported this indication. The panel based its vote on results of an open label pediatric study and extrapolation of efficacy data in adult studies to pediatric patients.

All but one panelist voted that safety concerns remained that still had not been adequately addressed, particularly with longterm treatment. Panelists were most concerned about the unclear risk of immunogenicity associated with treatment and the risk of malignancies, notably, a safety signal for hepatosplenic T-cell lymphoma (HSTCL).

Infliximab, a tumor necrosis factor blocker marketed as Remicade by Centocor Ortho Biotech, was previously approved by the FDA for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adults with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

The manufacturer had proposed that this indication be expanded to include pediatric patients, citing an open label, single arm, 54-week study of 60 pediatric patients (median age 14.5 years) with moderate to severe ulcerative colitis, and two adult studies. In the pediatric study, 73% (44 patients) at week 8 had a clinical response to infliximab, given at a dose of 5 mg/kg intravenously at weeks 0, 2 and 6. Responders were then randomized to one of two maintenance doses.

Over an average of 38 weeks of follow-up, 23% of the patients had serious adverse events, including infection (12%), anemia (1.7%), and neutropenia (1.7%). There were no cases of tuberculosis or malignancies, which have been reported in children treated with TNF-blockers.

HSTCL has been reported in people treated with infliximab who also have been treated or were currently undergoing treatment with a thiopurine (azathioprine and mercaptopurine), according to the manufacturer.

As of April 2008, 48 malignancies in children and adolescents treated with infliximab or other TNF antagonists have been reported to the FDA’s adverse event reporting system, of which 25 were in pediatric patients with Crohn’s disease (21) or ulcerative colitis (4). Among these 25 cases were 10 reports of HSTCL. There are no known cases of HSTCL in patients treated with a TNF antagonist without a history of previous or concomitant thiopurine treatment, according to the FDA.

Panelists stressed the importance of following patients closely for malignancies and other risks associated with infliximab treatment and informing patients and their parents about the possible serious risks of treatment.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver. At this meeting two panelists were granted a waiver because of their expertise and the "paucity" of physicians on the committee with knowledge of the subject, according to the disclosure forms posted by the FDA before the meeting.

The vaccine for the upcoming influenza season will contain the same three strains included in this past season’s vaccine, the Food and Drug Administration announced July 18.

Photo Marti/Fotolia.com

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

In February, the FDA’s Vaccines and Related Biological Products Advisory Committee made a preliminary recommendation that the influenza vaccine include these three strains, based on information that included the latest influenza surveillance and epidemiology data; antigenic characteristics of virus isolates; and serologic responses to current vaccines.

"There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness," according to the FDA statement. "However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications."

Licensed vaccines include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement. On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

The vaccine for the upcoming influenza season will contain the same three strains included in this past season’s vaccine, the Food and Drug Administration announced July 18.

Photo Marti/Fotolia.com

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

In February, the FDA’s Vaccines and Related Biological Products Advisory Committee made a preliminary recommendation that the influenza vaccine include these three strains, based on information that included the latest influenza surveillance and epidemiology data; antigenic characteristics of virus isolates; and serologic responses to current vaccines.

"There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness," according to the FDA statement. "However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications."

Licensed vaccines include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement. On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

The vaccine for the upcoming influenza season will contain the same three strains included in this past season’s vaccine, the Food and Drug Administration announced July 18.

Photo Marti/Fotolia.com

In a statement, the FDA announced that it had approved the 2011-2012 influenza vaccine formulation, which will include the following strains: A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus), A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus.

This formulation will be used by the six manufacturers that are licensed to produce and distribute the influenza vaccine in the United States.

In February, the FDA’s Vaccines and Related Biological Products Advisory Committee made a preliminary recommendation that the influenza vaccine include these three strains, based on information that included the latest influenza surveillance and epidemiology data; antigenic characteristics of virus isolates; and serologic responses to current vaccines.

"There is always a possibility of a less than optimal match between the virus strains predicted to circulate and the virus strains that end up causing the most illness," according to the FDA statement. "However, even if the vaccine and the circulating strains are not an exact match, the vaccine may reduce the severity of the illness or may help prevent influenza-related complications."

Licensed vaccines include Afluria (CSL Limited); Fluarix (GlaxoSmithKline Biologicals); FluLaval (ID Biomedical Corporation); FluMist (MedImmune); Fluvirin (Novartis Vaccines and Diagnostics); and Fluzone, Fluzone High-Dose, and Fluzone Intradermal (Sanofi Pasteur).

Fluzone Intradermal was approved in May 2011, and is delivered intradermally with a very small needle and is for people aged 18-64 years, according to the FDA statement. On July 18, Sanofi Pasteur announced that the company has begun shipping the 2011-2012 Fluzone vaccine.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends annual influenza vaccinations for everyone aged 6 months and older.

According to the CDC, 5%-20% of the U.S. population develops influenza each year, resulting in more than 200,000 hospitalizations for influenza-related complications and 3,000-49,000 deaths.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

A significant increase in cardiovascular events in patients with permanent atrial fibrillation who are taking dronedarone in the PALLAS trial has led the drug’s manufacturer to suspend the phase IIIb study.

Dronedarone (Multaq), a benzofuran derivative that is a an analogue of amiodarone, is approved in the United States and the European Union for a different population of patients with AF, not those with permanent AF, and "the benefit-risk of Multaq remains unchanged in its approved indication in nonpermanent AF," the company said in a press release issued on July 7.

The Food and Drug Administration approved dronedarone in 2009 for reducing the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors who are in sinus rhythm or who will be cardioverted. (In the EU, it is indicated for clinically stable adults with a history of nonpermanent AF or with current nonpermanent AF, to prevent the recurrence of AF or to lower the ventricular rate.)

PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) was discontinued for enrolled patients with permanent AF.

The international phase IIIb study compared dronedarone 400 mg twice daily (the approved dose) to placebo in about 3,000 patients with permanent AF, who were over age 65 and had comorbidities such as previous myocardial infarction, documented coronary artery disease, previous stroke, symptomatic heart failure, or diabetes. Patients with New York Heart Association class IV or unstable NYHA class III heart failure were excluded.

The company stopped the study in response to recommendations made by the study’s operations and data monitoring committees, after a significant increase in cardiovascular events was observed among those in the dronedarone arm, according to the statement.

In the statement, the study’s coprincipal investigator, Dr. Stuart Connolly, director of the cardiology division and professor of medicine at McMaster University, Hamilton, Ont., said that the committee members were "very disappointed to discover that the hypothesis that dronedarone would improve major outcomes for this high-risk patient population has been refuted."

Patients enrolled in PALLAS had permanent AF and were more likely to have advanced vascular disease than patients in whom the drug is currently indicated, who have intermittent AF and most often do not have advanced vascular disease, Dr. Connolly said in an interview.

"The results of PALLAS do not bear directly on the patients on dronedarone for the approved indication," he noted. "So it is reasonable to continue those patients on dronedarone, and I would expect that they will still benefit from it in terms of reduced cardiovascular hospitalization."

About 70% of the patients enrolled in PALLAS had had permanent AF for more than 2 years, and about 70% had NYHA class I-III heart failure at baseline, which the Sanofi statement listed as other differences between these patients and the patients enrolled in the ATHENA study that supported the currently approved indication. (In the ATHENA study, fewer than 30% of patients had NYHA class I-III heart failure and none had permanent AF, the statement said).

This is not the first indication that dronedarone may not be suitable for sicker patients. Its label already includes a black box warning that says the drug is contraindicated in patients with NYHA class IV heart failure or NYHA class II-III heart failure with a recent decompensation requiring hospitalization or referral to a heart failure clinic. This warning was based on the results of another dronedarone study that was stopped early – the ANDROMEDA study – which found that mortality was increased among such patients who were given dronedarone, when compared with placebo.

Dr. Connolly said he has received grant support and consulting and lecture fees from Sanofi.

A significant increase in cardiovascular events in patients with permanent atrial fibrillation who are taking dronedarone in the PALLAS trial has led the drug’s manufacturer to suspend the phase IIIb study.

Dronedarone (Multaq), a benzofuran derivative that is a an analogue of amiodarone, is approved in the United States and the European Union for a different population of patients with AF, not those with permanent AF, and "the benefit-risk of Multaq remains unchanged in its approved indication in nonpermanent AF," the company said in a press release issued on July 7.

The Food and Drug Administration approved dronedarone in 2009 for reducing the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors who are in sinus rhythm or who will be cardioverted. (In the EU, it is indicated for clinically stable adults with a history of nonpermanent AF or with current nonpermanent AF, to prevent the recurrence of AF or to lower the ventricular rate.)

PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) was discontinued for enrolled patients with permanent AF.

The international phase IIIb study compared dronedarone 400 mg twice daily (the approved dose) to placebo in about 3,000 patients with permanent AF, who were over age 65 and had comorbidities such as previous myocardial infarction, documented coronary artery disease, previous stroke, symptomatic heart failure, or diabetes. Patients with New York Heart Association class IV or unstable NYHA class III heart failure were excluded.

The company stopped the study in response to recommendations made by the study’s operations and data monitoring committees, after a significant increase in cardiovascular events was observed among those in the dronedarone arm, according to the statement.

In the statement, the study’s coprincipal investigator, Dr. Stuart Connolly, director of the cardiology division and professor of medicine at McMaster University, Hamilton, Ont., said that the committee members were "very disappointed to discover that the hypothesis that dronedarone would improve major outcomes for this high-risk patient population has been refuted."

Patients enrolled in PALLAS had permanent AF and were more likely to have advanced vascular disease than patients in whom the drug is currently indicated, who have intermittent AF and most often do not have advanced vascular disease, Dr. Connolly said in an interview.

"The results of PALLAS do not bear directly on the patients on dronedarone for the approved indication," he noted. "So it is reasonable to continue those patients on dronedarone, and I would expect that they will still benefit from it in terms of reduced cardiovascular hospitalization."

About 70% of the patients enrolled in PALLAS had had permanent AF for more than 2 years, and about 70% had NYHA class I-III heart failure at baseline, which the Sanofi statement listed as other differences between these patients and the patients enrolled in the ATHENA study that supported the currently approved indication. (In the ATHENA study, fewer than 30% of patients had NYHA class I-III heart failure and none had permanent AF, the statement said).

This is not the first indication that dronedarone may not be suitable for sicker patients. Its label already includes a black box warning that says the drug is contraindicated in patients with NYHA class IV heart failure or NYHA class II-III heart failure with a recent decompensation requiring hospitalization or referral to a heart failure clinic. This warning was based on the results of another dronedarone study that was stopped early – the ANDROMEDA study – which found that mortality was increased among such patients who were given dronedarone, when compared with placebo.

Dr. Connolly said he has received grant support and consulting and lecture fees from Sanofi.

A significant increase in cardiovascular events in patients with permanent atrial fibrillation who are taking dronedarone in the PALLAS trial has led the drug’s manufacturer to suspend the phase IIIb study.

Dronedarone (Multaq), a benzofuran derivative that is a an analogue of amiodarone, is approved in the United States and the European Union for a different population of patients with AF, not those with permanent AF, and "the benefit-risk of Multaq remains unchanged in its approved indication in nonpermanent AF," the company said in a press release issued on July 7.

The Food and Drug Administration approved dronedarone in 2009 for reducing the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors who are in sinus rhythm or who will be cardioverted. (In the EU, it is indicated for clinically stable adults with a history of nonpermanent AF or with current nonpermanent AF, to prevent the recurrence of AF or to lower the ventricular rate.)

PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) was discontinued for enrolled patients with permanent AF.

The international phase IIIb study compared dronedarone 400 mg twice daily (the approved dose) to placebo in about 3,000 patients with permanent AF, who were over age 65 and had comorbidities such as previous myocardial infarction, documented coronary artery disease, previous stroke, symptomatic heart failure, or diabetes. Patients with New York Heart Association class IV or unstable NYHA class III heart failure were excluded.

The company stopped the study in response to recommendations made by the study’s operations and data monitoring committees, after a significant increase in cardiovascular events was observed among those in the dronedarone arm, according to the statement.

In the statement, the study’s coprincipal investigator, Dr. Stuart Connolly, director of the cardiology division and professor of medicine at McMaster University, Hamilton, Ont., said that the committee members were "very disappointed to discover that the hypothesis that dronedarone would improve major outcomes for this high-risk patient population has been refuted."

Patients enrolled in PALLAS had permanent AF and were more likely to have advanced vascular disease than patients in whom the drug is currently indicated, who have intermittent AF and most often do not have advanced vascular disease, Dr. Connolly said in an interview.

"The results of PALLAS do not bear directly on the patients on dronedarone for the approved indication," he noted. "So it is reasonable to continue those patients on dronedarone, and I would expect that they will still benefit from it in terms of reduced cardiovascular hospitalization."

About 70% of the patients enrolled in PALLAS had had permanent AF for more than 2 years, and about 70% had NYHA class I-III heart failure at baseline, which the Sanofi statement listed as other differences between these patients and the patients enrolled in the ATHENA study that supported the currently approved indication. (In the ATHENA study, fewer than 30% of patients had NYHA class I-III heart failure and none had permanent AF, the statement said).

This is not the first indication that dronedarone may not be suitable for sicker patients. Its label already includes a black box warning that says the drug is contraindicated in patients with NYHA class IV heart failure or NYHA class II-III heart failure with a recent decompensation requiring hospitalization or referral to a heart failure clinic. This warning was based on the results of another dronedarone study that was stopped early – the ANDROMEDA study – which found that mortality was increased among such patients who were given dronedarone, when compared with placebo.

Dr. Connolly said he has received grant support and consulting and lecture fees from Sanofi.