News From the FDA

Botox Approved for Limb Spasticity

OnabotulinumtoxinA (Botox, Allergan) received FDA approval for the treatment of upper limb spasticity in adults, following a series of clinical trials showing that injections of the neurotoxin could significantly improve the tone and function of the flexor muscles of the elbow, wrist, and fingers.

Such spasticity can develop—sometimes after a long delay—following a stroke, spinal cord injury, or traumatic brain injury, or in advanced multiple sclerosis or cerebral palsy. The approval did not extend to the use of Botox for nonflexural muscles of the upper limbs, spasticity in the legs, or treatment of fixed contracture, the FDA noted.

The most common side effects experienced by study subjects were nausea, fatigue, bronchitis, muscle weakness, and pain in the arms. A black box warning says that the effects of Botox may extend beyond the area of injection, resulting in temporary paralysis that could affect swallowing and breathing.

Myopathy Occurs With Simvastatin

The risk of myopathy is increased when the highest dose of simvastatin is used, according to the Food and Drug Administration, which is conducting a safety review of the statin.

In a statement, the FDA advises health care professionals to be aware of the potential increased risk of muscle injury associated with the 80-mg dose of simvastatin, when compared with lower doses of simvastatin and “possibly other statin drugs.” Although myopathy is a known side effect associated with all statins, this warning “highlights the greater risk of developing muscle injury, including rhabdomyolysis,” when patients use higher doses of simvastatin.

Simvastatin is marketed as Zocor and is also available as a generic formulation. The drug also is combined with ezetimibe (Vytorin) and with niacin (Simcor).

Preliminary data from more than 6,000 patients taking simvastatin for almost 7 years showed that 52 (0.9%) of patients on the 80-mg dose developed myopathy, compared with 1 patient (0.02%) on the 20-mg dose. Eleven patients (0.02%) taking the 80-mg dose developed rhabdomyolysis, but none in the low-dose group developed the condition.

Plavix Not for Poor Metabolizers

The FDA updated the labeling for clopidogrel to emphasize that new data definitively show that the antiplatelet agent is less effective—and may not work at all—in patients defined as “poor metabolizers.”

The agency, which is notifying physicians that testing is available for the genotypes that are associated with poor metabolism, stopped short of recommending that all patients receive such testing before starting a course of clopidogrel (Plavix, Sanofi-Aventis). An estimated 2%–14% of the population probably have those alleles and are poor metabolizers, according to the FDA.

The FDA urges physicians to consider use of other antiplatelet agents in poor metabolizers, such as ticlopidine (Ticlid) or prasugrel (Effient), or potentially increasing the clopidogrel dose. Prasugrel did not seem to have the same metabolism issue.

Lung Drug Gets Okay From Panel

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 9-3 to recommend approval of pirfenidone for the reduction in the decline of lung function in idiopathic pulmonary fibrosis (IPF). Those who voted in favor of approval agreed that the data on the drug showed that treatment was beneficial in slowing the progression of the disease.

Panelists said, however, that more data are needed to help identify which subsets of patients with IPF may benefit the most from treatment. The panel also recommended that safety of the drug should be monitored long term, possibly in a patient registry.

There is no FDA-approved treatment for IPF, a progressive, irreversible diffuse parenchymal lung disease of unknown etiology that is typically diagnosed after age 50. Approximately 100,000 people in the United States have the disease, according to pirfenidone's manufacturer, InterMune.

Panel Votes Yes on DBS for Seizures

The FDA's Neurological Devices Advisory Panel voted 7–5 to recommend approval, with conditions, of an implantable device that delivers electrical stimulation to the brain as an adjunctive treatment for adults with refractory seizures.

The panel reviewed the data from one study of 109 patients on the Deep Brain Stimulation (DBS) System for Epilepsy, manufactured by Medtronic, which provides bilateral stimulation of the anterior thalamic nucleus. The proposed indication for the device is as adjunctive therapy for reducing the frequency of seizures in adults with epilepsy characterized by partial-onset seizures that are refractory to antiepileptic medications.

Panel members voting in favor of approval agreed that the study provided adequate efficacy and safety data on the device in this patient population. Those voting against approval were satisfied with the safety data, but said they did not consider the efficacy data robust enough to support approval.

The components of the DBS system include a neurostimulator that connects to two leads that are implanted in the anterior nucleus of the thalamus. The same system is already approved for treating essential tremor of Parkinson's disease.

Safety of Insulin Pumps Reviewed

Members of the FDA's General Hospital and Personal Use Devices Panel agreed that although there are technological issues with insulin infusion pumps, these are outweighed by user-related issues.

During 2006–2009, the FDA received 16,849 reports of adverse events (including 310 deaths) associated with insulin pumps; most were reported by the manufacturers. The reports were far from complete: In most cases the problem with the pump was not described, and the cause of death had not been thoroughly evaluated, according to the FDA. The most common device problems were listed as unknown (20%), replace (9%), display of an error message (almost 5%), failure to deliver (3%), and repair (3%).

Of the 310 deaths, the most commonly listed causes were diabetic coma, hyperglycemia, hypoglycemia, diabetic ketoacidosis, and unresponsiveness. There were 29 deaths associated with a motor vehicle.

Botox Approved for Limb Spasticity

OnabotulinumtoxinA (Botox, Allergan) received FDA approval for the treatment of upper limb spasticity in adults, following a series of clinical trials showing that injections of the neurotoxin could significantly improve the tone and function of the flexor muscles of the elbow, wrist, and fingers.

Such spasticity can develop—sometimes after a long delay—following a stroke, spinal cord injury, or traumatic brain injury, or in advanced multiple sclerosis or cerebral palsy. The approval did not extend to the use of Botox for nonflexural muscles of the upper limbs, spasticity in the legs, or treatment of fixed contracture, the FDA noted.

The most common side effects experienced by study subjects were nausea, fatigue, bronchitis, muscle weakness, and pain in the arms. A black box warning says that the effects of Botox may extend beyond the area of injection, resulting in temporary paralysis that could affect swallowing and breathing.

Myopathy Occurs With Simvastatin

The risk of myopathy is increased when the highest dose of simvastatin is used, according to the Food and Drug Administration, which is conducting a safety review of the statin.

In a statement, the FDA advises health care professionals to be aware of the potential increased risk of muscle injury associated with the 80-mg dose of simvastatin, when compared with lower doses of simvastatin and “possibly other statin drugs.” Although myopathy is a known side effect associated with all statins, this warning “highlights the greater risk of developing muscle injury, including rhabdomyolysis,” when patients use higher doses of simvastatin.

Simvastatin is marketed as Zocor and is also available as a generic formulation. The drug also is combined with ezetimibe (Vytorin) and with niacin (Simcor).

Preliminary data from more than 6,000 patients taking simvastatin for almost 7 years showed that 52 (0.9%) of patients on the 80-mg dose developed myopathy, compared with 1 patient (0.02%) on the 20-mg dose. Eleven patients (0.02%) taking the 80-mg dose developed rhabdomyolysis, but none in the low-dose group developed the condition.

Plavix Not for Poor Metabolizers

The FDA updated the labeling for clopidogrel to emphasize that new data definitively show that the antiplatelet agent is less effective—and may not work at all—in patients defined as “poor metabolizers.”

The agency, which is notifying physicians that testing is available for the genotypes that are associated with poor metabolism, stopped short of recommending that all patients receive such testing before starting a course of clopidogrel (Plavix, Sanofi-Aventis). An estimated 2%–14% of the population probably have those alleles and are poor metabolizers, according to the FDA.

The FDA urges physicians to consider use of other antiplatelet agents in poor metabolizers, such as ticlopidine (Ticlid) or prasugrel (Effient), or potentially increasing the clopidogrel dose. Prasugrel did not seem to have the same metabolism issue.

Lung Drug Gets Okay From Panel

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 9-3 to recommend approval of pirfenidone for the reduction in the decline of lung function in idiopathic pulmonary fibrosis (IPF). Those who voted in favor of approval agreed that the data on the drug showed that treatment was beneficial in slowing the progression of the disease.

Panelists said, however, that more data are needed to help identify which subsets of patients with IPF may benefit the most from treatment. The panel also recommended that safety of the drug should be monitored long term, possibly in a patient registry.

There is no FDA-approved treatment for IPF, a progressive, irreversible diffuse parenchymal lung disease of unknown etiology that is typically diagnosed after age 50. Approximately 100,000 people in the United States have the disease, according to pirfenidone's manufacturer, InterMune.

Panel Votes Yes on DBS for Seizures

The FDA's Neurological Devices Advisory Panel voted 7–5 to recommend approval, with conditions, of an implantable device that delivers electrical stimulation to the brain as an adjunctive treatment for adults with refractory seizures.

The panel reviewed the data from one study of 109 patients on the Deep Brain Stimulation (DBS) System for Epilepsy, manufactured by Medtronic, which provides bilateral stimulation of the anterior thalamic nucleus. The proposed indication for the device is as adjunctive therapy for reducing the frequency of seizures in adults with epilepsy characterized by partial-onset seizures that are refractory to antiepileptic medications.

Panel members voting in favor of approval agreed that the study provided adequate efficacy and safety data on the device in this patient population. Those voting against approval were satisfied with the safety data, but said they did not consider the efficacy data robust enough to support approval.

The components of the DBS system include a neurostimulator that connects to two leads that are implanted in the anterior nucleus of the thalamus. The same system is already approved for treating essential tremor of Parkinson's disease.

Safety of Insulin Pumps Reviewed

Members of the FDA's General Hospital and Personal Use Devices Panel agreed that although there are technological issues with insulin infusion pumps, these are outweighed by user-related issues.

During 2006–2009, the FDA received 16,849 reports of adverse events (including 310 deaths) associated with insulin pumps; most were reported by the manufacturers. The reports were far from complete: In most cases the problem with the pump was not described, and the cause of death had not been thoroughly evaluated, according to the FDA. The most common device problems were listed as unknown (20%), replace (9%), display of an error message (almost 5%), failure to deliver (3%), and repair (3%).

Of the 310 deaths, the most commonly listed causes were diabetic coma, hyperglycemia, hypoglycemia, diabetic ketoacidosis, and unresponsiveness. There were 29 deaths associated with a motor vehicle.

Botox Approved for Limb Spasticity

OnabotulinumtoxinA (Botox, Allergan) received FDA approval for the treatment of upper limb spasticity in adults, following a series of clinical trials showing that injections of the neurotoxin could significantly improve the tone and function of the flexor muscles of the elbow, wrist, and fingers.

Such spasticity can develop—sometimes after a long delay—following a stroke, spinal cord injury, or traumatic brain injury, or in advanced multiple sclerosis or cerebral palsy. The approval did not extend to the use of Botox for nonflexural muscles of the upper limbs, spasticity in the legs, or treatment of fixed contracture, the FDA noted.

The most common side effects experienced by study subjects were nausea, fatigue, bronchitis, muscle weakness, and pain in the arms. A black box warning says that the effects of Botox may extend beyond the area of injection, resulting in temporary paralysis that could affect swallowing and breathing.

Myopathy Occurs With Simvastatin

The risk of myopathy is increased when the highest dose of simvastatin is used, according to the Food and Drug Administration, which is conducting a safety review of the statin.

In a statement, the FDA advises health care professionals to be aware of the potential increased risk of muscle injury associated with the 80-mg dose of simvastatin, when compared with lower doses of simvastatin and “possibly other statin drugs.” Although myopathy is a known side effect associated with all statins, this warning “highlights the greater risk of developing muscle injury, including rhabdomyolysis,” when patients use higher doses of simvastatin.

Simvastatin is marketed as Zocor and is also available as a generic formulation. The drug also is combined with ezetimibe (Vytorin) and with niacin (Simcor).

Preliminary data from more than 6,000 patients taking simvastatin for almost 7 years showed that 52 (0.9%) of patients on the 80-mg dose developed myopathy, compared with 1 patient (0.02%) on the 20-mg dose. Eleven patients (0.02%) taking the 80-mg dose developed rhabdomyolysis, but none in the low-dose group developed the condition.

Plavix Not for Poor Metabolizers

The FDA updated the labeling for clopidogrel to emphasize that new data definitively show that the antiplatelet agent is less effective—and may not work at all—in patients defined as “poor metabolizers.”

The agency, which is notifying physicians that testing is available for the genotypes that are associated with poor metabolism, stopped short of recommending that all patients receive such testing before starting a course of clopidogrel (Plavix, Sanofi-Aventis). An estimated 2%–14% of the population probably have those alleles and are poor metabolizers, according to the FDA.

The FDA urges physicians to consider use of other antiplatelet agents in poor metabolizers, such as ticlopidine (Ticlid) or prasugrel (Effient), or potentially increasing the clopidogrel dose. Prasugrel did not seem to have the same metabolism issue.

Lung Drug Gets Okay From Panel

The FDA's Pulmonary-Allergy Drugs Advisory Committee voted 9-3 to recommend approval of pirfenidone for the reduction in the decline of lung function in idiopathic pulmonary fibrosis (IPF). Those who voted in favor of approval agreed that the data on the drug showed that treatment was beneficial in slowing the progression of the disease.

Panelists said, however, that more data are needed to help identify which subsets of patients with IPF may benefit the most from treatment. The panel also recommended that safety of the drug should be monitored long term, possibly in a patient registry.

There is no FDA-approved treatment for IPF, a progressive, irreversible diffuse parenchymal lung disease of unknown etiology that is typically diagnosed after age 50. Approximately 100,000 people in the United States have the disease, according to pirfenidone's manufacturer, InterMune.

Panel Votes Yes on DBS for Seizures

The FDA's Neurological Devices Advisory Panel voted 7–5 to recommend approval, with conditions, of an implantable device that delivers electrical stimulation to the brain as an adjunctive treatment for adults with refractory seizures.

The panel reviewed the data from one study of 109 patients on the Deep Brain Stimulation (DBS) System for Epilepsy, manufactured by Medtronic, which provides bilateral stimulation of the anterior thalamic nucleus. The proposed indication for the device is as adjunctive therapy for reducing the frequency of seizures in adults with epilepsy characterized by partial-onset seizures that are refractory to antiepileptic medications.

Panel members voting in favor of approval agreed that the study provided adequate efficacy and safety data on the device in this patient population. Those voting against approval were satisfied with the safety data, but said they did not consider the efficacy data robust enough to support approval.

The components of the DBS system include a neurostimulator that connects to two leads that are implanted in the anterior nucleus of the thalamus. The same system is already approved for treating essential tremor of Parkinson's disease.

Safety of Insulin Pumps Reviewed

Members of the FDA's General Hospital and Personal Use Devices Panel agreed that although there are technological issues with insulin infusion pumps, these are outweighed by user-related issues.

During 2006–2009, the FDA received 16,849 reports of adverse events (including 310 deaths) associated with insulin pumps; most were reported by the manufacturers. The reports were far from complete: In most cases the problem with the pump was not described, and the cause of death had not been thoroughly evaluated, according to the FDA. The most common device problems were listed as unknown (20%), replace (9%), display of an error message (almost 5%), failure to deliver (3%), and repair (3%).

Of the 310 deaths, the most commonly listed causes were diabetic coma, hyperglycemia, hypoglycemia, diabetic ketoacidosis, and unresponsiveness. There were 29 deaths associated with a motor vehicle.