Dosing & Uses
Dosage Forms & Strengths
tablet: Schedule V
- 50mg
- 200mg
- 300mg
- 400mg
Partial Onset Seizures
Indicated as adjunctive therapy in partial onset seizures uncontrolled by current medications and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity
Initial: 100 mg PO q8hr; may increase dose at weekly intervals, not to exceed dosage increase of 150 mg/day/week
Optimize effective dosage between 200 mg 3 times daily (600 mg per day) to 400 mg 3 times daily (1,200 mg per day)
In controlled clinical trials, 400 mg q8hr (1,200 mg/day) showed limited improvement compared to 300 mg q8hr (900 mg/day) with an increase in adverse reactions and discontinuations
Renal Impairment
Mild renal impairment (CrCl 50-80 mL/min): AUC increased by 30%
Moderate/end-stage renal impairment
- CrCl <50 mL/min
- Initial: 50 mg PO q8hr; may increase at weekly intervals in increments of <150 mg/day
- Maximum dose: Not to exceed 200 mg PO q8hr
- Hemodialysis: Immediately following dialysis, administer a single supplemental dose; if breakthrough seizures occur toward end of hemodialysis, consider additional supplemental dose at the start of subsequent dialysis sessions
Hepatic impairment
Mild hepatic impairment (Child-Pugh 5-6): AUC not affected
Moderate impairment
- (Child-Pugh 7-9): AUC increased ~50%; decrease initial and maintenance doses by 50%
- Initial: 50 mg PO q8hr; may increase dose at weekly intervals, not to exceed dosage increase of 50 mg/day/week
- Maximum dose: Not to exceed 250 mg PO q8hr
Severe impairment
- (Child-Pugh >9): AUC increased ~100%; decrease initial and maintenance doses by 50%
- Initial: 50 mg PO q8hr; may increase dose at weekly intervals, not to exceed dosage increase of 50 mg/day/week
- Maximum dose: Not to exceed 200 mg PO q8hr
Dosing Considerations
May cause retinal abnormalities with long-term use; therefore, treatment should be discontinued if patients fail to show substantial clinical benefit after adequate titration
Testing of visual function should be done at baseline and every 6 months during therapy
If retinal pigmentary abnormalities or vision changes are detected, discontinue unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss
<18 years: Safety and efficacy not established
Partial Onset Seizures
Initial: 50 mg PO q8hr; may increase dose at weekly intervals, not to exceed dosage increase of 50 mg/day/week
Maximum dose: Not to exceed 250 mg PO q8hr
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (16)
- adagrasib
adagrasib, ezogabine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
- dofetilide
dofetilide increases toxicity of ezogabine by QTc interval. Avoid or Use Alternate Drug. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- entrectinib
ezogabine and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole and ezogabine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
- glasdegib
ezogabine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate and ezogabine both increase QTc interval. Avoid or Use Alternate Drug.
- inotuzumab
inotuzumab and ezogabine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- ivosidenib
ivosidenib and ezogabine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
- lefamulin
lefamulin and ezogabine both increase QTc interval. Avoid or Use Alternate Drug.
- mobocertinib
mobocertinib and ezogabine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.
- ondansetron
ezogabine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
- panobinostat
ezogabine and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. Panobinostat is known to significantly prolong QT interval. Panobinostat prescribing information states use with drugs known to prolong QTc is not recommended.
- pitolisant
ezogabine and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.
- ribociclib
ribociclib increases toxicity of ezogabine by QTc interval. Avoid or Use Alternate Drug. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- umeclidinium bromide/vilanterol inhaled
ezogabine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
- vilanterol/fluticasone furoate inhaled
ezogabine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
Monitor Closely (103)
- amiodarone
ezogabine, amiodarone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- amisulpride
amisulpride and ezogabine both increase QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- amitriptyline
ezogabine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- amoxapine
ezogabine, amoxapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- apomorphine
ezogabine, apomorphine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- arsenic trioxide
ezogabine, arsenic trioxide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- artemether/lumefantrine
ezogabine, artemether/lumefantrine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- asenapine
ezogabine, asenapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- asenapine transdermal
asenapine transdermal and ezogabine both increase QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- azithromycin
ezogabine, azithromycin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- bedaquiline
ezogabine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely
- brexanolone
brexanolone, ezogabine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- chlorpromazine
ezogabine, chlorpromazine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ciprofloxacin
ezogabine, ciprofloxacin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- citalopram
ezogabine, citalopram. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- clarithromycin
ezogabine, clarithromycin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- clomipramine
ezogabine, clomipramine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- dasatinib
ezogabine, dasatinib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- degarelix
ezogabine, degarelix. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- desipramine
ezogabine, desipramine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- deutetrabenazine
ezogabine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- digoxin
ezogabine increases levels of digoxin by decreasing renal clearance. Use Caution/Monitor. Active metabolite, NAMR, may inhibit the renal tubular secretion. Monitor digoxin levels.
- disopyramide
ezogabine, disopyramide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- dofetilide
ezogabine, dofetilide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- dolasetron
ezogabine, dolasetron. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- dronedarone
ezogabine, dronedarone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- droperidol
ezogabine, droperidol. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- erythromycin base
ezogabine, erythromycin base. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- erythromycin ethylsuccinate
ezogabine, erythromycin ethylsuccinate. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- erythromycin lactobionate
ezogabine, erythromycin lactobionate. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- erythromycin stearate
ezogabine, erythromycin stearate. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- escitalopram
ezogabine, escitalopram. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
escitalopram increases toxicity of ezogabine by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval. - esketamine intranasal
esketamine intranasal, ezogabine. Either increases levels of the other by sedation. Use Caution/Monitor.
- flecainide
ezogabine, flecainide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- fluconazole
ezogabine, fluconazole. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- fluoxetine
ezogabine and fluoxetine both increase QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- foscarnet
ezogabine, foscarnet. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- fostemsavir
ezogabine and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- ganaxolone
ezogabine and ganaxolone both increase sedation. Use Caution/Monitor.
- gemifloxacin
ezogabine, gemifloxacin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- gemtuzumab
ezogabine and gemtuzumab both increase QTc interval. Use Caution/Monitor.
- goserelin
goserelin increases levels of ezogabine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.
- haloperidol
ezogabine, haloperidol. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- histrelin
histrelin increases toxicity of ezogabine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.
- hydroxyzine
hydroxyzine and ezogabine both increase QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed, particularly when dose titrated to 1200mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ibutilide
ezogabine, ibutilide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- iloperidone
ezogabine, iloperidone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- indapamide
ezogabine, indapamide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- isradipine
ezogabine, isradipine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- lapatinib
ezogabine, lapatinib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- lemborexant
ezogabine, lemborexant. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
- lenvatinib
ezogabine and lenvatinib both increase QTc interval. Use Caution/Monitor. Lenvatinib prescribing information recommends monitoring ECG closely when coadministered with QT prolonging drugs.
- leuprolide
leuprolide increases toxicity of ezogabine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.
- levofloxacin
ezogabine, levofloxacin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- lopinavir
ezogabine, lopinavir. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- lumefantrine
ezogabine, lumefantrine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- maprotiline
ezogabine, maprotiline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- mefloquine
ezogabine, mefloquine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- methadone
ezogabine, methadone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- methylphenidate transdermal
methylphenidate transdermal will increase the level or effect of ezogabine by decreasing metabolism. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.
- mifepristone
mifepristone, ezogabine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.
- moxifloxacin
ezogabine, moxifloxacin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- nilotinib
ezogabine, nilotinib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- nortriptyline
ezogabine, nortriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- octreotide
ezogabine, octreotide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ofloxacin
ezogabine, ofloxacin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- orlistat
orlistat decreases levels of ezogabine by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.
- osilodrostat
osilodrostat and ezogabine both increase QTc interval. Use Caution/Monitor.
- osimertinib
osimertinib and ezogabine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.
- ozanimod
ozanimod and ezogabine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
- paliperidone
ezogabine, paliperidone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- pasireotide
ezogabine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.
- pazopanib
ezogabine, pazopanib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- pentamidine
ezogabine, pentamidine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- pimozide
ezogabine, pimozide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- posaconazole
ezogabine, posaconazole. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- procainamide
ezogabine, procainamide. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- propafenone
ezogabine, propafenone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- protriptyline
ezogabine, protriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- quetiapine
ezogabine, quetiapine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- quinidine
ezogabine, quinidine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- quinine
ezogabine, quinine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ranolazine
ezogabine, ranolazine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- risperidone
ezogabine, risperidone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ritonavir
ezogabine, ritonavir. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- romidepsin
ezogabine, romidepsin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- saquinavir
ezogabine, saquinavir. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- selpercatinib
selpercatinib increases toxicity of ezogabine by QTc interval. Use Caution/Monitor.
- sorafenib
sorafenib and ezogabine both increase QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed, particularly when ezogabine dose titrated to 1200mg/day.
- sotalol
ezogabine, sotalol. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- sunitinib
ezogabine, sunitinib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- tacrolimus
ezogabine, tacrolimus. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- telavancin
ezogabine, telavancin. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- thioridazine
ezogabine, thioridazine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- thiothixene
ezogabine, thiothixene. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- toremifene
ezogabine, toremifene. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- trimipramine
ezogabine, trimipramine. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- triptorelin
triptorelin increases toxicity of ezogabine by QTc interval. Use Caution/Monitor. Increases risk of torsades de pointes.
- vandetanib
ezogabine, vandetanib. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- voclosporin
voclosporin, ezogabine. Either increases effects of the other by QTc interval. Use Caution/Monitor.
- voriconazole
ezogabine, voriconazole. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- vorinostat
ezogabine, vorinostat. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
- ziprasidone
ezogabine, ziprasidone. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.
Minor (6)
- carbamazepine
carbamazepine decreases levels of ezogabine by Mechanism: unknown. Minor/Significance Unknown. Upon discontinuation of carbamazepine, ezogabine clearance decreased by approximately 30%. Consider an increase in the ezogabine dose during concurrent use.
- chloroquine
chloroquine increases toxicity of ezogabine by QTc interval. Minor/Significance Unknown.
- clonazepam
ezogabine decreases levels of clonazepam by Other (see comment). Minor/Significance Unknown. Comment: Ezogabine may induce glucuronidation that results in small decreases of trough levels.
- lamotrigine
ezogabine decreases levels of lamotrigine by Other (see comment). Minor/Significance Unknown. Comment: Ezogabine may induce glucuronidation that results in small decreases of trough levels.
- phenytoin
phenytoin decreases levels of ezogabine by Mechanism: unknown. Minor/Significance Unknown. Upon discontinuation of phenytoin, ezogabine clearance decreased by approximately 30%. Consider an increase in the ezogabine dose during concurrent use.
- valproic acid
ezogabine decreases levels of valproic acid by Other (see comment). Minor/Significance Unknown. Comment: Ezogabine may induce glucuronidation that results in small decreases of trough levels.
Adverse Effects
In 3 controlled clinical studies, 25% of patients receiving ezogabine (199/813) and 11% of patients receiving placebo (45/427) discontinued treatment because of treatment-emergent adverse reactions
>10%
Dizziness (23%)
Somnolence (22%)
Fatigue (15%)
1-10%
Confusion (9%)
Vertigo (8%)
Tremor (8%)
Nausea (7%)
Abnormal coordination (7%)
Diplopia (7%)
Attention disturbance (6%)
Memory impairment (6%)
Asthenia (5%)
Blurred vision (5%)
Gait disturbance (4%)
Aphasia (4%)
Dysarthria (4%)
Balance disorder (4%)
Anxiety (3%)
Paresthesia (3%)
Infections (3%)
Weight gain (3%)
Constipation (3%)
Disorientation (2%)
Dyspepsia (2%)
Dysuria (2%)
Urinary retention/hesitation (2%)
Hematuria (2%)
Chromaturia (2%)
Hallucinations (2%)
Amnesia (2%)
Dysphasia (2%)
<1%
Psychotic disorder
Postmarketing Reports
Acquired vitelliform lesions
Warnings
Black Box Warnings
Can cause retinal abnormalities with funduscopic features similar to those seen in retinal pigment dystrophies, which are known to result in damage to the photoreceptors and vision loss
Some patients with retinal abnormalities have been found to have abnormal visual acuity; unknown if ezogabine caused this vision loss
Rate of progression of retinal abnormalities and their reversibility are unknown; about 33% of patients who had eye examinations performed after 4 yr of treatment were found to have retinal pigmentary abnormalities; an earlier onset cannot be ruled out
Discontinue if patient fails to show substantial clinical benefit after adequate titration
All patients should have baseline and periodic (every 6 months) systematic visual monitoring by an ophthalmic professional; testing should include visual acuity and dilated fundus photography
If retinal pigmentary abnormalities or vision changes are detected, discontinue ezogabine unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss
Contraindications
Hypersensitivity
Cautions
Slight and transient QT-prolongation observed; caution when administered with concomitant drugs that prolong QT interval, congenital long QT syndrome, heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia
Can cause retinal abnormalities (see Black Box Warnings)
Caution with existing conditions that may cause urinary retention; monitor for urologic symptoms
Monitor for confusional state, psychotic symptoms, or hallucinations
Monitor for dizziness and somnolence
Monitor for suicidal thoughts or behavior
Phenytoin or carbamazepine may decrease ezogabine serum levels
Macular abnormalities characterized as vitelliform lesions observed; lesions may also be seen in macular degenerative and dystrophic disorders
N-acetyl metabolite of ezogabine (NAMR) may inhibit renal clearance of digoxin, a P-gp substrate; monitor digoxin levels
Skin discoloration
- Can cause skin discoloration that is generally described as blue, but has also been described as grey-blue or brown
- Discoloration occurs predominantly on or around the lips or in the nail beds of the fingers or toes, but more widespread involvement of the face and legs has also been reported
- Discoloration of the palate, sclera, and conjunctiva has also been reported
- ~10% of patients in long-term clinical trials developed skin discoloration, generally after ≥2 yr of treatment and at higher doses (≥900 mg/day)
Pregnancy & Lactation
Pregnancy Category: C; based on animal data, may cause fetal harm (developmental toxicity)
North American Antiepileptic Drug (NAAED) Pregnancy Registry: 1-888-233-2334
Lactation: Unknown whether distributed in human breast milk; excreted in milk of lactating rats
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Antiseizure agent; neuronal potassium channel opener
Stabilizes neuronal KCNQ (Kv7) channels in the open position, increasing the stabilizing membrane current and preventing bursts of action potentials during the sustained depolarizations associated with seizures
May also augment gamma-aminobutyric acid (GABA) mediated neurotransmission
Pharmacokinetics
Bioavailability: ~60%
Peak Plasma Time: 0.5-2 hr (variable and may be lower in fasted stated)
Protein Bound: 80% (when concentration ranges between 0.1-2 mcg/mL); 45% (NAMR active metabolite)
Vd: 2-3 L/kg following IV
Metabolized by N-glucuronidation (primarily (UGT1A4) and N-acetylation (primarily NAT2)
Not a substrate, inducer, or inhibitor of CYP3A4 isoenzymes
Ezogabine is neither a substrate nor an inhibitor of the P-glycoprotein transporter and would not be expected to interact with drugs which are either P-glycoprotein inhibitors or substrates
Metabolites: Primary metabolites of ezogabine were the N2- and N4-glucuronides of ezogabine, the N-acetyl metabolite of ezogabine (NAMR) and the N2- and N4-glucuronides of NAMR
NAMR is not expected to have any impact on the overall pharmacological activity/safety of administered ezogabine
NAMR may inhibit the renal tubular secretion of digoxin, resulting in increased serum levels
Elimination
- Half-life: 7-11 hr (similar for both parent drug and active metabolite)
- Total body clearance: 0.4-0.6 L/hr/kg
- Excretion: feces (14%), urine (85%)
Administration
Oral Administration
Take orally in 3 equally divided doses with or without food
Swallow tablet whole, do not chew, split, or crush
When discontinuing, reduce dose gradually over at least 3 weeks, unless safety concerns require abrupt withdrawal
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Formulary
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