www.medscape.com/viewarti...411?src=mp
FDA Safety Labeling Changes: Vytorin and Topamax
Topiramate (Topamax) Linked to Risks of Metabolic Acidosis, Neuropsychiatric Adverse Events
On June 29, the FDA approved safety labeling revisions for topiramate (Topamax tablets and sprinkle capsules, made by Ortho-McNeil Pharmaceutical, Inc.) to advise of new clinical trial data regarding the risks of metabolic acidosis and neuropsychiatric adverse events associated with its use.
According to data from adult studies, 32% of patients receiving 400 mg/day of topiramate for adjunctive treatment of epilepsy experienced persistent treatment-emergent decreases in serum bicarbonate levels (levels < 20mEq/L at two consecutive visits or at final visit) compared with 1% of those receiving placebo. In patients receiving topiramate monotherapy, doses of 50 mg/day and 400 mg/day were associated with metabolic acidosis incidences of 15% and 25%, respectively.
In addition, 3% of adults receiving 400 mg/day of topiramate adjunctive therapy experienced an abnormally low serum bicarbonate level (absolute value < 17 mEq/L and > 5 mEq/L decrease from baseline) compared with no patients receiving placebo. The incidence in those receiving 50 mg/day and 400 mg/day of topiramate monotherapy was 1% and 7%, respectively.
Among pediatric patients younger than 16 years receiving topiramate therapy for adjunctive treatment of Lennox-Gastaut syndrome or refractory partial onset seizures, the incidence of persistent treatment-emergent decreases in serum bicarbonate was 67% (at approximately 6 mg/kg/day) vs 10% among placebo-treated children.
Topiramate 50 mg/day and 400 mg/day monotherapy in this population was linked to 7% and 20% incidences of metabolic acidosis, respectively; the incidence of abnormally low serum bicarbonate levels was 4% at both doses.
The FDA also noted that topiramate therapy is most commonly associated with central nervous systemrelated adverse events, including cognitive dysfunction, psychiatric/behavioral disturbances, and somnolence or fatigue.
According to new study data from a controlled trial of topiramate monotherapy in patients with epilepsy, one or more cognitive adverse events was reported in 19% and 26% of patients receiving topiramate 50 mg/day and 400 mg/day, respectively. The incidence of somnolence was also dose-related (50 mg/day, 9% vs 400 mg/day, 15%), and the rate of fatigue was comparable between groups (14%).
In pediatric clinical trials of topiramate, the incidence of neuropsychiatric adverse events was generally lower than that observed in adults.
In children receiving topiramate adjunctive therapy, the most frequently reported neuropsychiatric events were somnolence and fatigue; topiramate monotherapy was most commonly associated with headache, dizziness, anorexia, and somnolence.
Topiramate is indicated as initial monotherapy for partial onset or primary generalized tonic-clonic seizures in patients aged 10 years and older; as adjunctive therapy for partial onset or primary generalized tonic-clonic seizures in adults and pediatric patients aged two to 16 years; for the treatment of seizures associated with Lennox-Gastaut syndrome in patients aged two years and older; and for migraine prophylaxis in adults.
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I have heard reports that Topamax is referred to "on the street" as Stupomax or Dopamax because of its cognitive effects. Here are some first-person accounts:
groups.google.com/group/a...urce&hl=en
groups.google.com/group/a...urce&hl=en
Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.
www.ncbi.nlm.nih.gov/entr...query_hl=1
"CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function."
Mitigating cognitive side effects associated with topiramate.
www.ncbi.nlm.nih.gov/entr...query_hl=1
Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy.
www.ncbi.nlm.nih.gov/entr...query_hl=1
Severe topiramate-associated hyperthermia resulting in persistent neurological dysfunction.
www.ncbi.nlm.nih.gov/entr...query_hl=1
FDA Safety Labeling Changes: Vytorin and Topamax
Topiramate (Topamax) Linked to Risks of Metabolic Acidosis, Neuropsychiatric Adverse Events
On June 29, the FDA approved safety labeling revisions for topiramate (Topamax tablets and sprinkle capsules, made by Ortho-McNeil Pharmaceutical, Inc.) to advise of new clinical trial data regarding the risks of metabolic acidosis and neuropsychiatric adverse events associated with its use.
According to data from adult studies, 32% of patients receiving 400 mg/day of topiramate for adjunctive treatment of epilepsy experienced persistent treatment-emergent decreases in serum bicarbonate levels (levels < 20mEq/L at two consecutive visits or at final visit) compared with 1% of those receiving placebo. In patients receiving topiramate monotherapy, doses of 50 mg/day and 400 mg/day were associated with metabolic acidosis incidences of 15% and 25%, respectively.
In addition, 3% of adults receiving 400 mg/day of topiramate adjunctive therapy experienced an abnormally low serum bicarbonate level (absolute value < 17 mEq/L and > 5 mEq/L decrease from baseline) compared with no patients receiving placebo. The incidence in those receiving 50 mg/day and 400 mg/day of topiramate monotherapy was 1% and 7%, respectively.
Among pediatric patients younger than 16 years receiving topiramate therapy for adjunctive treatment of Lennox-Gastaut syndrome or refractory partial onset seizures, the incidence of persistent treatment-emergent decreases in serum bicarbonate was 67% (at approximately 6 mg/kg/day) vs 10% among placebo-treated children.
Topiramate 50 mg/day and 400 mg/day monotherapy in this population was linked to 7% and 20% incidences of metabolic acidosis, respectively; the incidence of abnormally low serum bicarbonate levels was 4% at both doses.
The FDA also noted that topiramate therapy is most commonly associated with central nervous systemrelated adverse events, including cognitive dysfunction, psychiatric/behavioral disturbances, and somnolence or fatigue.
According to new study data from a controlled trial of topiramate monotherapy in patients with epilepsy, one or more cognitive adverse events was reported in 19% and 26% of patients receiving topiramate 50 mg/day and 400 mg/day, respectively. The incidence of somnolence was also dose-related (50 mg/day, 9% vs 400 mg/day, 15%), and the rate of fatigue was comparable between groups (14%).
In pediatric clinical trials of topiramate, the incidence of neuropsychiatric adverse events was generally lower than that observed in adults.
In children receiving topiramate adjunctive therapy, the most frequently reported neuropsychiatric events were somnolence and fatigue; topiramate monotherapy was most commonly associated with headache, dizziness, anorexia, and somnolence.
Topiramate is indicated as initial monotherapy for partial onset or primary generalized tonic-clonic seizures in patients aged 10 years and older; as adjunctive therapy for partial onset or primary generalized tonic-clonic seizures in adults and pediatric patients aged two to 16 years; for the treatment of seizures associated with Lennox-Gastaut syndrome in patients aged two years and older; and for migraine prophylaxis in adults.
****************
I have heard reports that Topamax is referred to "on the street" as Stupomax or Dopamax because of its cognitive effects. Here are some first-person accounts:
groups.google.com/group/a...urce&hl=en
groups.google.com/group/a...urce&hl=en
Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.
www.ncbi.nlm.nih.gov/entr...query_hl=1
"CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function."
Mitigating cognitive side effects associated with topiramate.
www.ncbi.nlm.nih.gov/entr...query_hl=1
Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy.
www.ncbi.nlm.nih.gov/entr...query_hl=1
Severe topiramate-associated hyperthermia resulting in persistent neurological dysfunction.
www.ncbi.nlm.nih.gov/entr...query_hl=1
