"The U.S. Food and Drug Administration today approved a device to help reduce the frequency of seizures in epilepsy patients who have not responded well to medications.
The RNS Stimulator consists of a small neurostimulator implanted within "...
The following adverse reactions are described in more detail in the WARNINGS AND PRECAUTIONS section of the label:
- Retinal abnormalities and potential vision loss [see WARNINGS AND PRECAUTIONS]
- Urinary retention [see WARNINGS AND PRECAUTIONS]
- Skin discoloration [see WARNINGS AND PRECAUTIONS]
- Neuro-psychiatric symptoms [see WARNINGS AND PRECAUTIONS]
- Dizziness and somnolence [see WARNINGS AND PRECAUTIONS]
- QT interval effect [see WARNINGS AND PRECAUTIONS]
- Suicidal behavior and ideation [see WARNINGS AND PRECAUTIONS]
- Withdrawal seizures [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions and for varying durations, adverse reaction frequencies observed in the clinical trials of a drug cannot be directly compared with frequencies in the clinical trials of another drug and may not reflect the frequencies observed in practice.
POTIGA was administered as adjunctive therapy to 1,365 patients with epilepsy in all controlled and uncontrolled clinical studies during the premarketing development. A total of 801 patients were treated for at least 6 months, 585 patients were treated for 1 year or longer, and 311 patients were treated for at least 2 years.
Adverse Reactions Leading to Discontinuation in All Controlled Clinical Studies
In the 3 randomized, double-blind, placebo-controlled studies, 199 of 813 patients (25%) receiving POTIGA and 45 of 427 patients (11%) receiving placebo discontinued treatment because of adverse reactions. The most common adverse reactions leading to withdrawal in patients receiving POTIGA were dizziness (6%), confusional state (4%), fatigue (3%), and somnolence (3%).
Common Adverse Reactions in All Controlled Clinical Studies
Overall, the most frequently reported adverse reactions in patients receiving POTIGA ( ≥ 4% and occurring approximately twice the placebo rate) were dizziness (23%), somnolence (22%), fatigue (15%), confusional state (9%), vertigo (8%), tremor (8%), abnormal coordination (7%), diplopia (7%), disturbance in attention (6%), memory impairment (6%), asthenia (5%), blurred vision (5%), gait disturbance (4%), aphasia (4%), dysarthria (4%), and balance disorder (4%). In most cases the reactions were of mild or moderate intensity.
Table 4: Adverse Reaction Incidence in
Placebo-Controlled Adjunctive Trials in Adult Patients With Partial Onset
Seizures (Adverse reactions in at least 2% of patients treated with POTIGA in
any treatment group and numerically more frequent than in the placebo group.)
|Body System /Adverse Reaction||Placebo
(N = 427)%
(N = 281)%
(N = 273)%
(N = 259)%
(N = 813)%
|Infections and infestations|
|Disturbance in attention||< 1||6||6||7||6|
|Balance disorder||< 1||3||3||5||4|
|Amnesia||< 1||< 1||3||3||2|
|Disorientation||< 1||< 1||< 1||5||2|
|Psychotic disorder||0||0||< 1||2||<1|
|Renal and urinary|
|Urinary hesitation||< 1||2||1||4||2|
|Chromaturia||< 1||< 1||2||3||2|
Other adverse reactions reported in these 3 studies in < 2% of patients treated with POTIGA and numerically greater than placebo were increased appetite, hallucinations, myoclonus, peripheral edema, hypokinesia, dry mouth, dysphagia, hyperhydrosis, urinary retention, malaise, and increased liver enzymes.
Most of the adverse reactions appear to be dose related (especially those classified as psychiatric and nervous system symptoms), including dizziness, somnolence, confusional state, tremor, abnormal coordination, memory impairment, blurred vision, gait disturbance, aphasia, balance disorder, constipation, dysuria, and chromaturia.
POTIGA was associated with dose-related weight gain, with mean weight increasing by 0.2 kg, 1.2 kg, 1.6 kg, and 2.7 kg in the placebo, 600 mg per day, 900 mg per day, and 1,200 mg per day groups, respectively.
Additional Adverse Reactions Observed During All Phase 2 and 3 Clinical Trials
Following is a list of adverse reactions reported by patients treated with POTIGA during all clinical trials: rash, nystagmus, dyspnea, leukopenia, muscle spasms, alopecia, nephrolithiasis, syncope, neutropenia, thrombocytopenia, euphoric mood, renal colic, coma, encephalopathy.
Comparison of Gender, Age, and Race
The overall adverse reaction profile of POTIGA was similar for females and males.
There are insufficient data to support meaningful analyses of adverse reactions by age or race. Approximately 86% of the population studied was Caucasian, and 0.8% of the population was older than 65 years.
Read the Potiga (ezogabine tablets) Side Effects Center for a complete guide to possible side effects
The potentially significant interactions between POTIGA and concomitant AEDs are summarized in Table 5.
Table 5: Significant Interactions Between POTIGA and
Concomitant Antiepileptic Drugs
|AED||Dose of AED (mg/day)||Dose of POTIGA (mg/day)||Influence of POTIGA on AED||Influence of AED on POTIGA||Dosage Adjustment|
|Carbamazepinea,b||600- 2,400||300-1,200||None||31% decrease in AUC, 23% decrease in Cmax||consider an increase in dosage of POTIGA when adding carbamazepinec|
|Phenytoina,b||120-600||300-1,200||None||34% decrease in AUC, 18% decrease in Cmax||consider an increase in dosage of POTIGA when adding phenytoinc|
|a Based on results of a Phase 2 study.
b Inducer for uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs).
c A decrease in dosage of POTIGA should be considered when carbamazepine or phenytoin is discontinued.[See CLINICAL PHARMACOLOGY]
Data from an in vitro study showed that the N-acetyl metabolite of ezogabine (NAMR) inhibited P-glycoprotein-mediated transport of digoxin in a concentration-dependent manner, indicating that NAMR may inhibit renal clearance of digoxin. Administration of POTIGA at therapeutic doses may increase digoxin serum concentrations. Serum levels of digoxin should be monitored [see CLINICAL PHARMACOLOGY].
Alcohol increased systemic exposure to POTIGA. Patients should be advised of possible worsening of ezogabine's general dose-related adverse reactions if they take POTIGA with alcohol [see CLINICAL PHARMACOLOGY].
Ezogabine has been shown to interfere with clinical laboratory assays of both serum and urine bilirubin, which can result in falsely elevated readings.
Drug Abuse And Dependence
POTIGA is a Schedule V controlled substance.
A human abuse potential study was conducted in recreational sedative-hypnotic abusers (n = 36) in which single oral doses of ezogabine (300 mg [n = 33], 600 mg [n = 34], 900 mg [n = 6]), the sedative-hypnotic alprazolam (1.5 mg and 3.0 mg), and placebo were administered. Euphoria-type subjective responses to the 300-mg and 600-mg doses of ezogabine were statistically different from placebo but statistically indistinguishable from those produced by either dose of alprazolam. Adverse events reported following administration of single oral doses of 300 mg, 600 mg, and 900 mg ezogabine given without titration included euphoric mood (18%, 21%, and 33%, respectively; 8% from placebo), hallucination (0%, 0%, and 17%, respectively; 0% from placebo) and somnolence (18%, 15%, and 67%, respectively; 15% from placebo).
In Phase 1 clinical studies, healthy individuals who received oral ezogabine (200 mg to 1,650 mg) reported euphoria (8.5%), feeling drunk (5.5%), hallucination (5.1%), disorientation (1.7%), and feeling abnormal (1.5%).
In the 3 randomized, double-blind, placebo-controlled Phase 2 and 3 clinical studies, patients with partial seizures who received oral ezogabine (300 mg to 1,200 mg) reported euphoric mood (0.5%) and feeling drunk (0.9%), while those who received placebo did not report either adverse event (0%).
In a 28-day physical dependence study in which rats received daily ezogabine administration, abrupt drug discontinuation produced behavioral changes that included piloerection, increases in high step gait, and tremors, compared to vehicle-treated animals. These data show that ezogabine produces a withdrawal syndrome indicative of physical dependence.
Read the Potiga Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 9/19/2013
Additional Potiga Information
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