Adult Dosing
Adjunctive therapy in partial-onset seizures
Adult patients
- Initial dose: 100 mg PO tid x 1 wk (300 mg/day); may titrate gradually at weekly intervals by no more than 50 mg PO tid (150 mg/day)
- Maintenance dose: 200-400 mg PO tid (600-1200 mg/day)
- Maximum dose: 400 mg PO tid (1200 mg/day)
Notes:- Tablets should be swallowed whole
- Discontinue gradually over a period of minimum 3 weeks, unless safety concerns require abrupt withdrawal
Geriatric patients (>65 years)
- Initial dose: 50 mg PO tid (150 mg/day)
- Maintenance dose: Titrate to maintenance dosage by gradually increasing the dose at weekly intervals by no more than 50 mg PO tid (150 mg/day)
- Maximum dose: 250 mg PO tid (750 mg/day)
Notes:- Tablets should be swallowed whole
- Discontinue gradually over a period of minimum 3 weeks, unless safety concerns require abrupt withdrawal
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustment (Based on CrCl)
- Mild renal impairment: No dose adjustments
- <50 mL/min or end-stage renal disease on dialysis
- Initial dose: 50 mg PO tid (150 mg/day)
- Titration: Increase dosage at weekly intervals by no more than 50 mg PO tid (150 mg/day)
- Maximum dose: 200 mg PO tid (600 mg/day)
Hepatic Dose Adjustment
- Mild hepatic impairment: No dose adjustments
- Child-Pugh 7-9
- Initial dose: 50 mg PO tid (150 mg/day)
- Titration: Increase dosage at weekly intervals by no more than 50 mg PO tid (150 mg/day)
- Maximum dose: 250 mg PO tid (750 mg/day)
- Child-Pugh >9
- Initial dose: 50 mg PO tid (150 mg/day)
- Titration: Increase dosage at weekly intervals by no more than 50 mg PO tid (150 mg/day)
- Maximum dose: 200 mg PO tid (600 mg/day)
See Supplemental Patient Information
- Therapy may cause retinal abnormalities with long-term use. Discontinue the treatment if patients fail to show substantial clinical benefit after adequate titration. Examine visual function at baseline and every 6 months during therapy [FDA Black Box Warning]
- If retinal pigmentary abnormalities or vision changes are detected, therapy should be discontinued unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss [FDA Black Box Warning]
- Consider dose adjustment in geriatric patients and patients with moderate to severe renal or hepatic impairment
- Increased risk of urinary retention has been reported with this drug; closely monitor urologic symptoms in patients receiving therapy. Carefully monitor patients who have other risk factors for urinary retention (e.g., benign prostatic hyperplasia), patients unable to communicate clinical symptoms (e.g., cognitively impaired patients), or patients on concomitant medications that may affect voiding (e.g., anticholinergics). A comprehensive evaluation of urologic symptoms prior to and during therapy is recommended in these patients
- Therapy may cause skin discoloration: If a patient develops skin discoloration, serious consideration should be given to an alternative treatment
- Confusional state, psychotic symptoms, and hallucinations have been reported with this drug. Rapid titration at greater than recommended doses increases the risk of psychosis and hallucinations
- Therapy with this drug may cause dose-related increases in dizziness and somnolence; these adverse reactions were mild to moderate in intensity and occurred during the titration phase
- Ezogabine has been associated with prolongation of QT interval. Monitoring QT interval is recommended when prescribing concomitantly with drugs known to increase QT interval and in patients with known prolonged QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia
- Ezogabine may increase the risk of suicidal thoughts or behavior in patients receiving these drugs for any indication. Monitor these patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
- Discontinue gradually to minimize the risk of increased seizure frequency
- Serum levels of digoxin should be monitored when co-administered with ezogabine, as it may increase digoxin serum concentrations
Supplemental Patient Information
- Inform patients that therapy may cause urinary retention including urinary hesitation and dysuria; advise patients to seek immediate medical assistance if they experience any symptoms of urinary retention, inability to urinate, and pain with urination
- Instruct patients and their caregivers to promptly report their physicians if they experience psychotic symptoms
- Inform patients, their caregivers, and families that therapy may increase the risk of suicidal thoughts and behavior; advise them of the need to be alert for the emergence or worsening of symptoms of depression; any unusual changes in mood or behavior; or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Instruct them to report any such behaviors of concern immediately to healthcare providers
- Inform patients that concomitant alcohol consumption may increase systemic exposure to this drug leading to worsening of the drug's dose-related adverse reactions
- Advise patients not to drive, operate complex machinery, or engage in other hazardous activities during therapy
Pregnancy Category:C
Breastfeeding: It is unknown whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, manufacturer recommends that a decision should be made to discontinue nursing or to discontinue the drug, analyzing the importance of the drug to the mother.
