Ezogabine (retigabine)

Potiga (U.S.) / Trobalt (EU) · Discontinued

Historical antiseizure indications · Discontinued

Indication / use

Label / evidence summary: Discontinued. Historical Potiga indication: adjunctive focal-onset seizures in adults ≥18 years who responded inadequately to several alternatives and for whom benefits outweighed retinal / vision risks.
Role: Historical maintenance use · Discontinued
Class: Potassium-channel opener

Historical reference only. The linked FDA PDF is an archived label, not a current DailyMed product label. Discontinued marketing status does not by itself establish the reason for discontinuation or withdrawal of approval.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Potiga tablets (Discontinued) Discontinued · historical U.S. label
Focal seizures · 18 years and older (historical label) · Maintenance
Historical restricted adjunctive use after several alternatives proved inadequate; retinal risks required specific benefit–risk assessment.
- Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Formulations & strengths

Archived U.S. label; historical strengths, not current availability.

Tablet (Potiga; Discontinued)

Strengths: 50, 200, 300, 400 mg
Product note: Historical U.S. strengths; Trobalt is the former EU brand.

Brand & formulation labels

Each link names the product and formulation it covers. Archived labels do not establish current availability.

Dosing & administration

Adult / product-specific schedule: Historical label: start 100 mg three times daily; increase at weekly intervals by no more than 50 mg per dose (150 mg/day total). Maintenance 200–400 mg three times daily (600–1,200 mg/day). The highest dose had limited added benefit and more adverse effects versus 900 mg/day.
Pediatric: Historical U.S. indication was adults 18 years and older; pediatric safety and effectiveness were not established.
Titration / repeat dosing: Historical dosing only. Taper over at least 3 weeks unless a safety concern requires faster withdrawal. For age ≥65, start 50 mg three times daily; maximum 250 mg three times daily.
Dose basis: Historical archived-label dosing for a discontinued drug; included for reference, not current prescribing.

Practical administration

Product instructions: Historical label: swallow tablets whole; take with or without food in three equal daily doses.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Dose adjustment & concentrations

Renal impairment: Historical label for creatinine clearance <50 mL/min or hemodialysis: start 50 mg three times daily; maximum 200 mg three times daily. Dialysis required specific supplemental-dose instructions in the label.
Hepatic impairment: Historical label: Child-Pugh 7–9, start 50 mg three times daily and maximum 250 mg three times daily; Child-Pugh >9, same starting dose and maximum 200 mg three times daily.
Serum reference information: No established therapeutic serum range is supplied in the cited label.

Safety

Boxed warning: Retinal abnormalities with potential vision loss. Archived label required baseline and 6-monthly ophthalmic monitoring, with discontinuation considered for retinal pigmentation or vision changes.
Contraindications: None listed in the archived U.S. label; this does not remove its boxed warning or major precautions.
Serious precautions & monitoring: Retinal and skin pigmentation, vision loss, urinary retention, neuropsychiatric symptoms, QT prolongation, dizziness / somnolence and suicidal thoughts or behavior.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Common / selected adverse effects

Dizziness
Somnolence
Fatigue
Confusion / impaired coordination
Blurred vision

Selected label-reported effects; frequencies cannot be compared across drugs.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Drug interactions: toxicity & clinical action

Partner / combination	Clinical effect	Clinical action
Carbamazepine / phenytoin	May lower ezogabine exposure.	Historical label advises considering a dose increase; reassess when the interacting drug is withdrawn.
Digoxin	N-acetyl metabolite may inhibit renal digoxin transport.	Monitor digoxin concentrations.
Alcohol / other sedatives	Increased ezogabine exposure with alcohol and/or additive CNS impairment.	Review combined exposure and impairment risk.
QT-prolonging drugs	Potential additive QT risk.	Review ECG and risk factors under specialist supervision.

Selected interactions; consult the full label and complete medication list.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Pregnancy & contraception

Fetal / neonatal risk: Inadequate human pregnancy data; animal studies showed developmental toxicity at clinically relevant exposures. Archived label requires assessment of potential fetal harm.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Clinical evidence

Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.

Direct pivotal trial

Trial summary

Study design / duration: RESTORE 1: randomized, double-blind, placebo-controlled adjunctive trial; 305 treated adults; 18-week treatment period.
Primary endpoint: Percentage change in focal-seizure frequency
Results: At 1,200 mg/day, median focal-seizure reduction was 44.3% versus 17.5% with placebo. At least 50% reduction occurred in 44.4% versus 17.8%; adverse-event discontinuations were 26.8% versus 8.6%. This historical trial does not imply current product availability.

PubMed · RESTORE 1 randomized trial ↗

Trial publications

PubMed · RESTORE 1 randomized trial ↗

Comparative evidence

Findings: No head-to-head efficacy comparison is summarized.

PubMed · RESTORE 1 randomized trial ↗

Mechanism of action

In vitro, enhances potassium currents through KCNQ (Kv7.2–Kv7.5) channels, stabilizing resting membrane potential and reducing excitability.
The archived label also describes possible augmentation of GABA-mediated currents; the therapeutic mechanism is not fully established.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Pharmacology

Adult values unless specified. Vd/F denotes apparent oral distribution volume.

Pharmacokinetics

Bioavailability: Approximately 60% absolute oral bioavailability.
Elimination half-life: Ezogabine and its N-acetyl metabolite have similar elimination half-lives of 7–11 hours.
Volume of distribution: Steady-state volume of distribution 2–3 L/kg after IV dosing.
Active metabolite(s): N-acetyl metabolite (NAMR) has antiseizure activity but is less potent in animal models; major N-glucuronides are inactive.
Active-metabolite half-life: N-acetyl metabolite: 7–11 hours.
Protein binding: Ezogabine approximately 80%; N-acetyl metabolite approximately 45%.
Metabolism / elimination: Mainly glucuronidation and acetylation; renal elimination predominates. No oxidative CYP-mediated metabolism demonstrated in the label’s in-vitro studies.

Values reflect the cited product and study population; they are not interchangeable across formulations.

Potiga — archived FDA label, 2016 (PDF; Discontinued) ↗

Molecular structure

Principal compound; salt and product forms may differ.
NIH PubChem structure and record ↗

Product history

Initial U.S. approval: June 10, 2011 — Potiga (NDA 022345)
Market / formulation history: All U.S. Potiga strengths are listed as Discontinued. EMA records withdrawal of Trobalt’s EU authorization on July 19, 2018, at the holder’s request for commercial reasons.
Brands: Potiga (U.S.) / Trobalt (EU) · Discontinued
Manufacturer / marketer: GlaxoSmithKline in the archived Potiga label
Generic availability: No currently marketed U.S. product is identified in the cited FDA application.
Related drugs: Other KCNQ-channel modulators under investigation are separate compounds and do not inherit this approval.

Sources & review status

Archived FDA label and product marketing status checked: 2026-09-27. Other profile sources reviewed: 2026-09-27 · label revision noted at that review: Archived FDA Potiga label: May 2016.. This is a draft reference; final review is pending.