ezogabine (Rx)

Brand and Other Names:Potiga

Dosing & Uses

AdultPediatricGeriatric

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

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Interactions

Interaction Checker

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              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.

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              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

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              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)
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              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.

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              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%)
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              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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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.