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Ezogabine

Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: [2-Amino-4-[[(4-fluoro-phenyl)methyl]amino]phenyl]-ethyl ester carbamic acid
Molecular Formula: C16H18FN3O2
CAS Number: 150812-12-7
Brands: Potiga

Warning(s)

  • Risk of retinal abnormalities and potential vision loss; characterized by funduscopic features similar to those seen in retinal pigment dystrophies known to cause photoreceptor damage and vision loss.1 (See Ocular Effects under Cautions.)

  • Abnormal visual acuity also reported in some patients with retinal abnormalities; however, a causal relationship to the drug not established.1

  • Rate of progression and potential for reversibility not known.1

  • Discontinue therapy in patients who fail to show substantial clinical benefit after adequate titration.1

  • 1 Periodic visual monitoring by an ophthalmic professional required at baseline and every 6 months thereafter.1

  • If retinal pigment abnormalities or vision changes are detected, discontinue ezogabine therapy unless no other suitable treatment options are available and the benefits of the drug outweigh the potential risk of vision loss.1

REMS:

FDA approved a REMS for ezogabine to ensure that the benefits outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Anticonvulsant; a neuronal potassium channel opener.1 2 3 4 6 7 8 9 13 14 15 16 17 19 20 22

Uses for Ezogabine

Seizure Disorders

Management (in combination with other anticonvulsants) of partial-onset seizures in adults who have not responded to alternative therapies and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity.1 2 3 4 8 31 (See Ocular Effects under Cautions.)

Ezogabine Dosage and Administration

General

  • Withdraw ezogabine gradually (i.e., by reducing dosage over ≥3 weeks) to minimize the potential for increased seizure frequency, unless concerns for patient safety require more rapid withdrawal.1 (See Discontinuance of Therapy under Cautions.)

  • Because of risk of retinal abnormalities with long-term use, discontinue therapy if patient fails to show substantial clinical benefit after adequate dosage titration.1 (See Ocular Effects under Cautions.)

  • Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 (See Suicidality Risk under Cautions.)

  • Therapeutic drug monitoring not required.9

Administration

Oral Administration

Administer orally with or without food.1 Divide total daily dosage into 3 equal doses.1

Swallow tablets whole; do not break, crush, dissolve, or chew.1

Dosage

Adults

Seizure Disorders
Partial Seizures
Oral

Initially, 300 mg daily (given as 100 mg 3 times daily).1

Increase by increments of no more than 150 mg daily (given as 50 mg 3 times daily) at weekly intervals up to a maintenance dosage of 600–1200 mg daily (given as 200–400 mg 3 times daily) based on patient response and tolerability.1

In controlled clinical studies, a maintenance dosage of 1200 mg daily appeared to provide limited benefit over 900 mg daily and was associated with increased adverse effects and drug discontinuance.1 4

Rapid titration at greater than recommended dosages may increase risk of psychosis and hallucinations.1 (See Neuropsychiatric Effects under Cautions.)

Concomitant use of carbamazepine and/or phenytoin may require adjustment of ezogabine dosage.1 (See Specific Drugs and Laboratory Tests under Interactions.)

Prescribing Limits

Adults

Seizure Disorders
Partial Seizures
Oral

Safety and efficacy of dosages >1200 mg daily not established.1 4 7

Special Populations

Hepatic Impairment

Mild (Child-Pugh score 5–6) hepatic impairment: No dosage adjustment required.1

Moderate (Child-Pugh score 7–9) hepatic impairment: Initially, 50 mg 3 times daily.1 Increase at weekly intervals by increments of no more than 50 mg 3 times daily up to a maximum maintenance dosage of 250 mg 3 times daily based on patient response and tolerability.1

Severe (Child-Pugh score >9) hepatic impairment: Initially, 50 mg 3 times daily.1 Increase at weekly intervals by increments of no more than 50 mg 3 times daily up to a maximum maintenance dosage of 200 mg 3 times daily based on patient response and tolerability.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Mild renal impairment (Clcr ≥50–80 mL/minute): No dosage adjustment required.1

Moderate to severe renal impairment (Clcr <50 mL/minute) and end-stage renal disease requiring hemodialysis: Initially, 50 mg 3 times daily.1 Increase at weekly intervals by increments of no more than 50 mg 3 times daily up to a maximum maintenance dosage of 200 mg 3 times daily based on patient response and tolerability.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Patients ≥65 years of age: Initially, 50 mg 3 times daily.1 May increase at weekly intervals by no more than 50 mg 3 times daily up to a maximum maintenance dosage of 250 mg 3 times daily based on patient response and tolerability.1 (See Geriatric Use under Cautions.)

Gender or Race

Dosage adjustment not required.1

Cautions for Ezogabine

Contraindications

  • None.1

Warnings/Precautions

Warnings

Ocular Effects

Retinal abnormalities with funduscopic features (e.g., perivascular pigmentation in retinal periphery, focal retinal pigment epithelium clumping) similar to retinal pigment dystrophies reported.1 35 (See Boxed Warning.) Observed with long-term (approximately 4 years) use of ezogabine, but an earlier onset cannot be excluded.1 Abnormal visual acuity also reported in some patients.1

Retinal abnormalities have occurred in conjunction with skin discoloration; however, not clear whether these effects are related.1 (See Dermatologic Effects under Cautions.)

Use only in patients who have not responded adequately to alternative therapies and for whom the benefits outweigh the risk of retinal abnormalities and potential vision loss.1 Discontinue therapy in patients who fail to show substantial clinical benefit.1

Perform eye examinations at baseline and every 6 months thereafter; include visual acuity testing and dilated fundus photography with additional tests (e.g., fluorescein angiograms, optical coherence tomography, perimetry, electroretinograms) as necessary.1 34 35 (See Advice to Patients.)

If retinal pigment changes or any vision changes are observed, discontinue drug unless no other treatment options are available and benefits outweigh risks.1 34 35 (See Discontinuance of Therapy under Cautions.)

Other Warnings/ Precautions

Urinary Retention

Urinary retention and related adverse effects (e.g., urinary hesitation, dysuria, chromaturia [usually reddish-brown], urinary tract infection) reported, generally within first 6 months of therapy but may occur later.1 2 3 6 8 9 20 27 33 Symptoms generally mild to moderate in severity and usually resolve spontaneously or upon drug discontinuance; however, some patients required catheterization.1 3 6 27 Hydronephrosis reported rarely.1 33

Assess risk of urinary retention, including medical history and concomitant drug use, before initiating therapy.33 Carefully monitor all patients for urologic symptoms (e.g., urinary retention, urinary hesitation, dysuria) during therapy (see Advice to Patients).1 20 24 27 33

Closer monitoring is recommended in patients with other risk factors (e.g., benign prostatic hyperplasia [BPH]), patients unable to communicate symptoms (e.g., cognitively impaired patients), and those concurrently receiving drugs that may affect voiding (e.g., anticholinergic agents).1 27 33 Consider comprehensive evaluation of urologic symptoms prior to and during therapy in such patients.1 27 33

Dermatologic Effects

Skin discoloration, generally described as blue, but also as gray-blue or brown, reported.1 Predominately appears around lips or in nail beds of fingers or toes; however, more widespread involvement of the face and legs also reported.1 34 38 Scleral and conjunctival discoloration also observed.1 34 Such effects were generally reported after ≥2 years of ezogabine therapy and at higher dosages.1 In some cases, retinal abnormalities occurred in conjunction with skin discoloration.1 (See Ocular Effects under Cautions.)

Appears to be a cosmetic effect; however, possibility of more extensive systemic involvement has not been excluded.1 34

If skin discoloration develops, seriously consider alternative therapy.1 34 Potential for reversibility after drug discontinuance not known.1

Neuropsychiatric Effects

Dose-related adverse neuropsychiatric effects, including confusional state, psychosis, and hallucinations, reported.1 3 4 6 8 Generally occurred within the first 8 weeks of treatment and resolved within 7 days of drug discontinuance.1 Hospitalization was required in some patients who experienced psychosis or hallucinations.1

Monitor for confusional state, psychotic symptoms, and hallucinations (see Advice to Patients).1

Dizziness and Somnolence

Dizziness and somnolence, which are dose related, commonly reported; generally mild to moderate in severity.1 2 3 4 6 7 8 20 Generally occur during the titration period and diminish with continued use of drug.1 3 6 7

Monitor for dizziness and somnolence.1 (See Advice to Patients.)

Prolongation of QT Interval

QT-interval prolongation observed in healthy individuals receiving ezogabine.1 Clinically important effects on the corrected QT (QTc) interval not reported to date in epileptic patients receiving the drug.6 8 20

Monitor ECG for QT-interval prolongation in patients with preexisting prolonged QT interval, CHF, ventricular hypertrophy, hypokalemia, or hypomagnesemia and in those concurrently receiving drugs known to prolong the QT interval.1 (See Drugs that Prolong QT Interval under Interactions.)

Suicidality Risk

Increased risk of suicidality (suicidal behavior or ideation) observed in an analysis of studies using various anticonvulsants in patients with epilepsy, psychiatric disorders (e.g., bipolar disorder, depression, anxiety), and other conditions (e.g., migraine, neuropathic pain); risk in patients receiving anticonvulsants (0.43%) was approximately twice that in patients receiving placebo (0.24%).1 10 11 12 Increased suicidality risk was observed ≥1 week after initiation of anticonvulsant therapy and continued through 24 weeks.1 10 11 Risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1 10

Closely monitor all patients currently receiving or beginning anticonvulsant therapy for changes in behavior that may indicate emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 Anxiety, agitation, hostility, insomnia, and mania may be precursors to emerging suicidality.10

Balance risk of suicidality with risk of untreated illness.1 10 Epilepsy and other illnesses treated with anticonvulsants are themselves associated with morbidity and mortality and an increased risk of suicidality.1 12 If suicidal thoughts or behavior emerges during anticonvulsant therapy, consider whether these symptoms may be related to the illness itself.1 12 (See Advice to Patients.)

Discontinuance of Therapy

Abrupt withdrawal of anticonvulsants may result in increased seizure frequency.1 When discontinuing ezogabine therapy, reduce dosage gradually (e.g., over ≥3 weeks).1 (See General under Dosage and Administration.)

Abuse Potential and Dependence

Ezogabine is subject to control as a schedule V (C-V) drug.1 5 Because of pharmacologic similarity, abuse potential is expected to be similar to that of other schedule V drugs (e.g., pregabalin, lacosamide).5

Data from animal studies indicate that physical dependence (with withdrawal effects after abrupt discontinuance) also can occur.1 Because euphoria has been reported, psychological dependence also may occur.1

Specific Populations

Pregnancy

Category C.1

North American Antiepileptic Drug (NAAED) Pregnancy Registry (for patients) at 888-233-2334 or .1

Effects on labor and delivery are unknown.1

Lactation

Not known whether distributed into human milk; ezogabine and/or its metabolites distribute into milk in rats.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

Insufficient experience in geriatric patients ≥65 years of age to establish efficacy and safety.1

Because of possible decreased clearance in geriatric patients, administer reduced initial and maintenance dosages.1 27 32 (See Geriatric Patients under Dosage and Administration and also see Elimination: Special Populations, under Pharmacokinetics.)

May cause urinary retention.1 Possible increased risk of urinary retention in geriatric men with symptomatic BPH; closer monitoring recommended.1 Geriatric patients unable to communicate possible symptoms of urinary retention (e.g., cognitively impaired patients) also require closer monitoring.1 (See Urinary Retention under Cautions.)

Hepatic Impairment

Because of possible increased exposure, administer reduced dosages in patients with moderate (Child-Pugh score 7–9) or severe (Child-Pugh score >9) hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration and also see Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Because of possible increased exposure, administer reduced dosages in patients with moderate to severe (Clcr <50 mL/minute) renal impairment and in those with end-stage renal disease requiring hemodialysis.1 (See Renal Impairment under Dosage and Administration and also see Absorption: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Dizziness, somnolence, fatigue, confusional state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, memory impairment, asthenia, blurred vision, gait disturbance, aphasia, dysarthria, balance disorder.1 2 3 4 6 8

Interactions for Ezogabine

Neither ezogabine nor its active N-acetyl metabolite (NAMR) is metabolized by CYP enzymes in vitro.1

Does not appear to inhibit CYP1A2, 2A6, 2B6 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5.1 Ezogabine and its NAMR metabolite do not induce CYP1A2 and 3A4/5.1

Neither a substrate nor inhibitor of P-glycoprotein (P-gp); however, NAMR metabolite inhibits P-gp.1

Not an inhibitor of organic cation transporter (OCT) 2 or organic anion transporter (OAT) 1, but weak inhibitor of OAT 3.1

Metabolized by uridine diphosphate-glucuronosyltransferase (UGT) 1A4 and, to a lesser extent, by UGT1A1, 1A3, and 1A9.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes: Pharmacokinetic interactions unlikely.1

Drugs metabolized by major CYP isoenzymes: Pharmacokinetic interactions unlikely.1

Drugs Affected by the P-glycoprotein Transport System

P-gp substrates: Potential pharmacokinetic interaction (increased concentrations of substrate drug).1

Drugs Affecting Uridine Diphosphate-glucuronosyltransferase

UGT inducers: Potential pharmacokinetic interaction (decreased ezogabine concentrations).1

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT-interval prolongation).1 Monitor QT interval.1 (See Prolongation of QT Interval under Cautions.)

Protein-bound Drugs

Clinically important pharmacokinetic interactions unlikely.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Alcohol

Increased peak concentrations and AUC of ezogabine; increased incidence of blurred vision reported1 6 7

Possible additive CNS and other adverse effects associated with ezogabine1 6 7

Pharmacokinetics of alcohol not affected6

Advise patients that alcohol consumption may potentiate some dose-related adverse effects associated with ezogabine (e.g., somnolence, fatigue)1 6 7

Anesthetics, general (e.g., thiopental)

Animal studies suggest possible increased duration of anesthesia induced by some general anesthetics32

Antiarrhythmics (class Ia and III; e.g., amiodarone, dofetilide, quinidine, sotalol)

Increased risk of QT-interval prolongation1 18

Monitor ECG for QT-interval prolongation1

Anticholinergic agents

May increase risk of urinary retention1 27 33

Closely monitor; consider comprehensive evaluation of urologic symptoms before and during ezogabine therapy1 27 33

Antimicrobial agents that prolong QT interval (e.g., clarithromycin, erythromycin, moxifloxacin)

Increased risk of QT-interval prolongation1 18

Monitor ECG for QT-interval prolongation1

Antipsychotic agents that prolong QT interval (e.g., chlorpromazine, haloperidol, quetiapine, risperidone, thioridazine, ziprasidone)

Increased risk of QT-interval prolongation1 18

Monitor ECG for QT-interval prolongation1

Carbamazepine

Decreased peak concentrations and AUC of ezogabine; no change in carbamazepine pharmacokinetics1

Consider increase in ezogabine dosage when initiating carbamazepine; conversely, consider decrease in ezogabine dosage when discontinuing carbamazepine1

Clobazam

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Clonazepam

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Contraceptives, oral (ethinyl estradiol with norethindrone or norgestrel)

No substantial pharmacokinetic interaction observed1 6 7

Digoxin

Systemic exposure of digoxin increased by 8–18%1

No dosage adjustment necessary1

Gabapentin

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Lamotrigine

Increased clearance and decreased AUC of lamotrigine; increased half-life and AUC of ezogabine1 6 25

Observed effects considered to be modest16 25

No dosage adjustment necessary1

Levetiracetam

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Oxcarbazepine

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Phenobarbital

Pharmacokinetic interaction unlikely1 7 29

No dosage adjustment necessary1

Phenytoin

Decreased peak concentrations and AUC of ezogabine; no change in phenytoin pharmacokinetics1

Consider increase in ezogabine dosage when initiating phenytoin; conversely, consider decrease in ezogabine dosage when discontinuing phenytoin1

Pregabalin

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Tests for bilirubin in serum or urine

Falsely elevated concentrations possible1

Topiramate

No pharmacokinetic interaction observed1

No dosage adjustment necessary1

Valproic acid

No pharmacokinetic interaction observed1

No dosage adjustment necessary1

Zonisamide

No evidence of pharmacokinetic interaction based on population pharmacokinetic analysis1

No dosage adjustment necessary1

Ezogabine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations generally achieved within 0.5–2 hours.1 3 4 7 16 23 25 26 29 Exhibits dose-proportional, linear pharmacokinetics with no expected accumulation with repeated administration.1 23

Absolute bioavailability of oral ezogabine is approximately 60%.1

Food

Administration with a high-fat meal increased peak plasma concentrations by approximately 38% and delayed time to peak concentrations by 0.75 hour, but did not affect extent of absorption.1 3 4 6 7

Special Populations

Systemic exposure is increased by approximately 50% in individuals with moderate (Child-Pugh score 7–9) hepatic impairment and by approximately 100% in those with severe (Child-Pugh score >9) hepatic impairment.1 20 Systemic exposure not affected by mild (Child-Pugh score 5–6) hepatic impairment.1

Systemic exposure is increased by approximately 30% in individuals with mild renal impairment (Clcr 50–80 mL/minute) and by approximately 100% in those with moderate to severe renal impairment (Clcr <50 mL/minute).1 20

Distribution

Extent

Appears to be well distributed.1

Not known whether distributed into human milk; ezogabine and/or its metabolites distribute into milk in rats.1

Plasma Protein Binding

Ezogabine: Approximately 80%.1 7 16

Active NAMR metabolite: Approximately 45%.1

Elimination

Metabolism

Extensively metabolized in the liver via glucuronidation and acetylation; does not appear to undergo oxidative metabolism via CYP isoenzymes.1 6 7 16 21 22 28

Metabolized to inactive N-glucuronide conjugates by UGT1A1, 1A3, 1A4, and 1A9.1 21 28 Also converted to an N-acetyl (NAMR) metabolite, which is pharmacologically active but to a lesser extent than the parent drug.1 16 21

Elimination Route

Approximately 85% of an orally administered dose is recovered in urine as unchanged drug and metabolites, and 14% in feces mainly as metabolites.1 7 16 26

Half-life

Approximately 7–11 hours for both ezogabine and its NAMR metabolite.1 26

Special Populations

Clearance was reduced and elimination half-life prolonged (by about 30%) in healthy geriatric individuals compared with healthy younger adults.1 26 32 Such decreased clearance may be due, at least in part, to an age-related decline in renal function.6 20 26

Hemodialysis reduces plasma concentrations of ezogabine and its NAMR metabolite by approximately 50%.32

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).1

Actions

  • Anticonvulsant that acts primarily as a selective neuronal potassium channel opener; derivative of the centrally acting analgesic flupirtine.1 2 3 4 6 7 8 9 13 14 15 16 17 19 20 22

  • Exact mechanism of action not fully elucidated, but thought to reduce neuronal excitability by activating specific voltage-gated potassium channels in the brain known as the KCNQ (Kv7.2 to 7.5) family of ion channels.1 2 3 5 6 7 13 14 15 16 17 19 20

  • Minimal effect on cardiac Kv7.1 channels.9 15 20

  • Also shown to potentiate GABA-mediated neurotransmission at substantially higher than therapeutic dosages.1 4 5 7 15 17 20

Advice to Patients

  • Importance of providing patient with a copy of manufacturer's patient information (medication guide) when ezogabine treatment is begun and each time the drug is dispensed.1 33 Importance of patients reading the information carefully and discussing any questions with their clinician.1

  • Risk of retinal abnormalities and vision loss.1 34 35 Importance of patients obtaining baseline and periodic eye examinations during therapy.1 34 35 Advise patients to promptly contact their clinician if any vision changes occur.1 34

  • Risk of urinary retention, including urinary hesitation and dysuria.1 3 27 33 Advise patients of the need to maintain regular voiding3 and to seek immediate medical assistance if any symptoms of urinary retention, inability to urinate, and/or pain with urination occurs.1 In patients who cannot reliably report symptoms of urinary retention (e.g., patients with cognitive impairment), urologic consultation may be helpful.1 27

  • Risk of discoloration of the nails, lips, palate, and parts of the eye.1 Advise patients to notify their clinician if any skin discoloration develops (usually reported after long-term therapy, but may occur earlier).1

  • Risk of psychiatric symptoms (e.g., confusional state, disorientation, hallucinations, other psychotic symptoms); advise patients and their caregivers to notify their clinician if any such symptoms occur.1

  • Risk of dizziness, somnolence, memory impairment, abnormal coordination/balance, attention disturbance, and ophthalmologic effects (e.g., diplopia, blurred vision), particularly during initiation of therapy and dosage titration.1 32 Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects.1 Advise patients that alcohol can increase the dose-related adverse effects of ezogabine.1 6 7

  • Risk of suicidality (anticonvulsants, including ezogabine, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 10 12 Importance of patients, family members, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one's life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 10

  • Advise patients not to abruptly discontinue therapy without consulting their clinician.1 Inform patients that sudden discontinuance of ezogabine can increase the risk of seizures.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of clinicians informing women about the existence of and encouraging enrollment in the NAAED Pregnancy Registry (see Pregnancy under Cautions).1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., enlarged prostate, kidney or liver disease, depression or other mood disorders, QT-interval prolongation) or family history of suicidality or bipolar disorder.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule V (C-V) drug.1 5

Ezogabine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

50 mg

Potiga ( C-V)

GlaxoSmithKline

200 mg

Potiga ( C-V)

GlaxoSmithKline

300 mg

Potiga ( C-V)

GlaxoSmithKline

400 mg

Potiga ( C-V)

GlaxoSmithKline

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

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3. French JA, Abou-Khalil BW, Leroy RF et al. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology. 2011; 76:1555-63. [PubMed 21451152]

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27. Brickel N, Gandhi P, VanLandingham K et al. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (Kv7) potassium channels. Epilepsia. 2012; 53:606-12. [PubMed 22428574]

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