ezogabine

ezogabine

(e-zoe-ga-been) ,

Potiga

(trade name)

Classification

Therapeutic: anticonvulsants
Pharmacologic: potassium channel openers
Pregnancy Category: C

Indications

Adjunctive treatment of partial-onset seizures.

Action

Enhances transmembrane potassium currents (enhances KCNQ channels), stabilizes resting membrane potential and decreases excitability. May also increase GABA-mediated currents.

Therapeutic effects

Decreased occurrence of partial-onset seizures.

Pharmacokinetics

Absorption: Well absorbed (60%) following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized, one metabolite (NAMR) has anti-epileptic activity; 36% excreted unchanged in urine.
Half-life: 7–11 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown0.5–2 hr8 hr

Contraindications/Precautions

Contraindicated in: Lactation: Breastfeeding not recommended.
Use Cautiously in: History of prolonged QT interval, concurrent use of medications know to prolong QT interval, history of HF, ventricular hypertrophy, hypokalemia or hypomagnesemia (↑ risk of arrhythmias); History of depression, suicidal thoughts or ideation; Geriatric: Lower doses recommended; Renal impairment (dose ↓ recommended for CCr <50 mL/min; Obstetric: Use only if potential benefit justifies potential risk to the fetus; Pediatric: Safety and effectiveness use not established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • drowsiness (most frequent)
  • aphasia
  • confusion
  • dysarthria
  • fatigue
  • hallucinations
  • impaired attention
  • impaired memory
  • psychoses
  • suicidal thoughts/ideation

Ear, Eye, Nose, Throat

  • blurred vision
  • conjunctival discoloration
  • diplopia
  • retinal pigment changes
  • scleral discoloration

Neurologic

  • abnormal coordination
  • balance disorder
  • gait disturbance
  • tremor

Genitourinary

  • urinary retention

Dermatologic

  • blue skin discoloration

Miscellaneous

  • physical dependence

Interactions

Drug-Drug interaction

Blood levels and effectiveness may be ↓ by carbamazepine or phenytoin ; larger doses may be required. One metabolite may ↓ excretion of digoxin ; monitoring is recommended. Concurrent use of alcohol ↑ blood levels and risk of adverse reactions.

Route/Dosage

Oral (Adults) 100 mg 3 times daily for 1 wk, then ↑ by 150 mg/day at weekly intervals to maintenance dose of 200–400 mg 3 times daily (not to exceed 1200 mg/day).
Oral (Geriatric Patients) 50 mg 3 times daily initially, then ↑ by 150 mg/day at weekly intervals to maintenance dose not to exceed 750 mg/day.

Renal Impairment

Oral (Adults) CCr <50 mL/min—50 mg 3 times daily initially, then ↑ by 150 mg/day at weekly intervals to maintenance dose not to exceed 600 mg/day.

Hepatic Impairment

Oral (Adults) Child-Pugh >7–9—50 mg 3 times daily initially, then ↑ by 150 mg/day at weekly intervals to maintenance dose not to exceed 750 mg/day; Child-Pugh >9—50 mg 3 times daily initially, then ↑ by 150 mg/day at weekly intervals to maintenance dose not to exceed 600 mg/day.

Availability

Tablets: 50 mg, 200 mg, 300 mg, 400 mg

Nursing implications

Nursing assessment

  • Assess location, duration, and characteristics of seizure activity. Institute seizure precautions. Assess response to and continued need for ezogabine periodically during therapy.
  • Monitor patient for signs and symptoms of urinary retention (inability to urinate, pain with urination), especially patients with increased risk (benign prostatic hyperplasia, patients unable to communicate symptoms, patients taking concomitant mediations that may affect voiding such as anticholinergics).
  • Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Obtain systematic visual monitoring, including visual acuity and dilated fundus photography, by an ophthalmologist at baseline and every 6 months during therapy. If abnormalities in pigment of retina or vision changes are detected, discontinue therapy unless benefits outweigh risks of potential vision loss.
  • Lab Test Considerations: May cause false ↑ in serum and urine bilirubin.

Potential Nursing Diagnoses

Risk for injury (Indications)

Implementation

  • Oral: Administer 3 times daily without regard to food. Swallow tablets whole; do not crush, break or chew.

Patient/Family Teaching

  • Instruct patient to take ezogabine around the clock, as directed. Medication should be gradually discontinued to prevent seizures. Advise patient to read the Medication Guide prior to taking ezogabine and with each Rx refill in case of changes.
  • May cause dizziness and drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Inform patients and families of risk of suicidal thoughts and behavior and advise that behavioral changes, emergency or worsening signs and symptoms of depression, unusual changes in mood, or emergence of suicidal thoughts, behavior, or thoughts of self-harm should be reported to health care professional immediately.
  • May cause grey-blue skin discoloration of lips, nail beds of fingers or toes, face, legs, and mucous membranes. Advise patient to notify health care professional if skin discoloration occurs; may require discontinuation of therapy.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient to avoid taking other CNS depressants or alcohol.
  • Emphasize the importance of regular eye examinations. Visual changes may require discontinuation of therapy.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.

Evaluation/Desired Outcomes

  • Decreased seizure activity.
Mentioned in ?
References in periodicals archive ?
Food and Drug Administration under the American brand name Ezogabine as an anticonvulsant, physicians may use it off label in stroke patients.
The anti-seizure drug ezogabine reduced alcohol consumption in an experimental model, report researchers from the Boston (Mass.
Washington, April 20 ( ANI ): A new study has found that anti-seizure drug ezogabine reduced alcohol consumption in an experimental model.
The animal data suggest risk if ezogabine (Potiga; C), an oral anticonvulsant indicated as adjunctive treatment of partial-onset seizures, is used in pregnancy.
Ezogabine has been approved as adjunctive therapy for partial onset seizures in adults but will not be available until later this year.
In a unanimous vote, a federal advisory panel agreed that the antiepileptic drug ezogabine had been shown to be effective as adjunctive therapy for partial onset seizures, but recommended that treated patients be closely monitored for the development of urinary retention.
This edition includes new drugs, including Azilsartan Medoxomil, Boceprevir, Clobazam, Ezogabine, Fidaxomicin, Linagliptin, Rilpivirine, Rivaroxaban, Telaprevir, Roflumilast, Ticagrelor, and Vilazodone; updated bisphosphonate, antipsychotic, carbapenem, and proton pump inhibitor group monographs; new combinations such as Emtricitabine/Rilpivirine/Tenofovir; and a revised ophthalmic/otic chapter with additions like glaucoma combinations, mast cell stabilizers, ophthalmic antihistamines, and otic corticosteroids.
Meda's partner for ezogabine - known as retigabine outside of the U.
today announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion, recommending marketing authorization for retigabine, named ezogabine in the US, as an adjunctive (add-on) treatment of partial onset seizures, with or without secondary generalisation in adults aged 18 years and above with epilepsy.
Valeant Pharmaceuticals International (NYSE: VRX) and GlaxoSmithKline plc (NYSE: GSK) recently announced that the US Food and Drug Administration (FDA) issued a complete response letter (CRL) for the new drug application (NDA) for their epilepsy candidate, ezogabine.
Valeant Pharmaceuticals International, (Meda's (STO:MEDAA) partner for ezogabine - known as retigabine outside of the U.