|
依佐加滨片Potiga(ezogabine,retigabine，瑞替加滨)(八)
<1
2
<1
Renal and urinary
Dysuria
<1
1
2
4
2
Urinary hesitation
<1
2
1
4
2
Hematuria
<1
2
1
2
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.
7 DRUG INTERACTIONS
7.1 Antiepileptic Drugs
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 (12.3)]
7.2 Digoxin
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 (12.3)].
7.3 Alcohol
Alcohol increased systemic exposure to POT |
|
