Version May 2024
Ezogabine 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. In addition, macular abnormalities characterized as vitelliform lesions have been observed. These lesions have been identified most consistently with optical coherence tomography imaging.
Some patients with retinal abnormalities have been found to have abnormal visual acuity. It is not possible to determine whether ezogabine caused this decreased visual acuity, because baseline assessments are not available for these patients.
Approximately one-third of the patients who had eye examinations performed after approximately 4 years of treatment were found to have retinal pigmentary abnormalities. An earlier onset cannot be ruled out, and it is possible that retinal abnormalities were present earlier in the course of exposure to ezogabine. The rate of progression of retinal abnormalities and their reversibility are unknown. Reversibility of retinal pigmentary abnormalities and partial resolution of vitelliform lesions has been reported after discontinuation of ezogabine in some patients.
Only use ezogabine in patients who have responded inadequately to several alternative treatments and for whom the benefits outweigh the potential risk of vision loss. Patients who fail to show substantial clinical benefit after adequate titration should be discontinued from ezogabine.
All patients taking ezogabine should have baseline and periodic (every 6 months) systematic visual monitoring by an ophthalmic professional. Testing should include visual acuity, dilated fundus photography, and optical coherence tomography. Additional testing may include fluorescein angiograms, perimetry, and electroretinograms (ERG).
If retinal pigmentary abnormalities or vision changes are detected, discontinue therapy unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss.
Note: Potiga has been discontinued in the United States for >1 year.
Partial-onset seizures, adjunct: Oral: Initial: 100 mg 3 times daily; may increase at weekly intervals in increments of ≤150 mg per day to a maintenance dose of 200 to 400 mg 3 times daily based on tolerability (maximum: 400 mg 3 times daily [1,200 mg per day]). In clinical trials, no additional benefit and an increase in adverse effects was observed with doses >900 mg per day. Note: If there is no substantial benefit after adequate titration, then discontinue use and consider other treatment options.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Initial: 50 mg 3 times daily; may increase at weekly intervals in increments of ≤150 mg per day to a maximum dose of 200 mg 3 times daily (600 mg per day).
ESRD requiring hemodialysis: Initial: 50 mg 3 times daily; may increase at weekly intervals in increments of ≤150 mg per day to a maximum dose of 200 mg 3 times daily (600 mg per day). Note: Immediately following hemodialysis a single supplemental dose is recommended; if break through seizures occur toward the end of hemodialysis, an additional supplemental dose may be considered at the start of subsequent dialysis sessions.
Mild impairment (Child-Pugh 5 to 6): No dosage adjustment necessary.
Moderate impairment (Child-Pugh 7 to 9): Initial: 50 mg 3 times daily; may increase at weekly intervals in increments of ≤150 mg per day to a maximum dose of 250 mg 3 times daily (750 mg per day).
Severe impairment (Child-Pugh >9): Initial: 50 mg 3 times daily; may increase at weekly intervals in increment of ≤150 mg per day to a maximum dose of 200 mg 3 times daily (600 mg per day).
Partial-onset seizures, adjunct: Oral: Initial: 50 mg 3 times daily; may increase at weekly intervals in increments of ≤150 mg per day to a maximum dose of 250 mg 3 times daily (750 mg per day). Note: If there is no substantial benefit after adequate titration, then discontinue use and consider other treatment options.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Central nervous system: Dizziness (dose related; 15% to 32%), drowsiness (dose related; 15% to 27%), fatigue (13% to 16%), confusion (dose related; 4% to 16%), ataxia (dose related; 5% to 12%)
Neuromuscular & skeletal: Tremor (dose related; 10% to 12%)
2% to 10%:
Central nervous system: Vertigo (8% to 9%), memory impairment (dose related; 6% to 9%), dysarthria (2% to 8%), lack of concentration (6% to 7%), aphasia (dose related; 1% to 7%), abnormal gait (dose related; 2% to 6%), disorientation (5%), anxiety (3% to 5%), equilibrium disturbance (dose related; 3% to 5%), paresthesia (3% to 5%), amnesia (3%), dysphasia (1% to 3%), hallucination (≤2%), psychotic symptoms (≤2%)
Dermatologic: Skin discoloration (10%)
Endocrine & metabolic: Weight gain (dose related; 2% to 3%)
Gastrointestinal: Nausea (6% to 9%), constipation (dose related; 4% to 5%), dyspepsia (3%)
Genitourinary: Dysuria (dose related; 1% to 4%), urinary hesitancy (1% to 4%), urine discoloration (dose related; 2% to 3%), urinary retention (≤2%), hematuria (1% to 2%)
Infection: Influenza (4% to 5%)
Neuromuscular & skeletal: Weakness (4% to 6%)
Ophthalmic: Blurred vision (dose related; 4% to 10%), diplopia (6% to 8%)
Frequency not defined:
Cardiovascular: Prolonged QT interval on ECG (mean: 7.7 msec), syncope
Central nervous system: Brain disease, coma, euphoria
Dermatologic: Alopecia, skin rash
Hematologic & oncologic: Leukopenia, neutropenia, thrombocytopenia
Neuromuscular & skeletal: Muscle spasm
Ophthalmic: Nystagmus, retinal pigment changes
Renal: Nephrolithiasis, renal colic
Respiratory: Dyspnea
<2%, postmarketing, and/or case reports: Dysphagia, hydronephrosis, hyperhidrosis, hypokinesia, increased appetite, increased liver enzymes, maculopathy (acquired vitelliform lesions), malaise, mucosal discoloration, myoclonus, nail discoloration, ocular discoloration (sclera), peripheral edema, suicidal ideation, suicidal tendencies, xerostomia
There are no contraindications listed in the manufacturer’s labeling.
Concerns related to adverse effects:
• CNS effects: Dose-related dizziness and somnolence (generally mild-to-moderate) have been reported; effects generally occur during dose titration and appear to diminish with continued use. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Dermatologic effects: Skin discoloration has been reported; typically blue in color (but may also be gray-blue or brown) and is predominantly located on or around the lips, nail beds of the fingers or toes, face and legs; discoloration of the palate, sclera, and conjunctiva may also occur. Skin discoloration developed in ~10% of patients, generally after ≥2 years of treatment and at higher doses (≥900 mg). If detected, consider other treatment options or discontinue use.
• Neuropsychiatric disorders: Dose-related neuropsychiatric disorders, including confusion, psychotic symptoms, and hallucinations, have been reported, generally within the first 8 weeks of treatment; some patients required hospitalization. Symptoms resolved in most patients within 7 days of discontinuation of therapy. The risk appears to be greatest with rapid titration at greater than the recommended doses.
• Ocular complications: [US Boxed Warning]: Retinal abnormalities that may progress to vision loss have been reported and were seen in about one-third of patients after approximately 4 years of treatment. These retinal abnormalities exhibited funduscopic features similar to those of retinal pigment dystrophies. Macular abnormalities characterized as vitelliform lesions have also been observed; these lesions have been identified most consistently with optical coherence tomography imaging. The rate of progression and reversibility of these retinal abnormalities is unknown. Reversibility of retinal pigmentary abnormalities and partial resolution of vitelliform lesions has been reported after discontinuation of ezogabine. Limit use to patients who have responded inadequately to other treatments and in whom the benefits of therapy exceed the risk of vision loss. Visual monitoring (at least visual acuity, dilated fundus photography, and optical coherence tomography) by an ophthalmic professional is recommended at baseline and at 6-month intervals. Other visual tests may include fluorescein angiograms, perimetry, and electroretinograms). Discontinue use if there is no substantial benefit after adequate titration or if retinal pigmentary abnormalities or vision changes are detected. If no other treatment options are available and the benefits of treatment outweigh the potential risk of vision loss, then may cautiously continue treatment with ezogabine.
• QT prolongation: QT prolongation has been observed; monitor ECG in patients with electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), concomitant medications which may augment QT prolongation, or any underlying cardiac abnormality which may also potentiate risk (eg, heart failure, ventricular hypertrophy).
• Suicidal thinking/behavior: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
• Urinary retention: Urinary retention, including retention requiring catheterization, has been reported, generally within the first 6 months of treatment. All patients should be monitored for urologic symptoms; close monitoring is recommended in patients with other risk factors for urinary retention (eg, benign prostatic hyperplasia), patients unable to communicate clinical symptoms, or patients who use concomitant medications that may affect voiding (eg, anticholinergics).
Disease-related concerns:
• Hepatic impairment: Dosage adjustment recommended in moderate to severe hepatic impairment; ezogabine exposure increases in moderate to severe impairment.
• Renal impairment: Dosage adjustment recommended in patients with CrCl <50 mL/minute renal impairment or patients with end-stage renal disease receiving hemodialysis; ezogabine undergoes significant renal elimination.
Special populations:
• Older adult: Use caution in elderly due to potential for urinary retention, particularly in older men with symptomatic BPH. Systemic exposure is increased in the elderly; dosage adjustment is recommended in patients ≥65 years of age.
Other warnings/precautions:
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency. Unless safety concerns require a more rapid withdrawal, therapy should be withdrawn gradually over a period of ≥3 weeks to minimize the potential of increased seizure frequency.
Potiga has been discontinued in the US for more than 1 year.
No
Tablets (Potiga Oral)
50 mg (90): $651.53
200 mg (90): $1303.02
300 mg (90): $1303.02
400 mg (90): $1303.02
Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single manufacturer of the brand and/or generic product, respectively. The pricing data should be used for benchmarking purposes only, and as such should not be used to set or adjudicate any prices for reimbursement or purchasing functions. Pricing data is updated monthly.
C-V
Administer in 3 equally divided doses daily with or without food. Swallow tablets whole; do not break, crush, dissolve, or chew. If therapy is discontinued, gradually reduce dose over at least 3 weeks unless safety concerns require abrupt withdrawal.
An FDA-approved patient medication guide, which is available with the product information and at https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Potiga/pdf/POTIGA-MG.PDF, must be dispensed with this medication.
Partial-onset seizures: As adjunctive treatment for partial-onset seizures in patients ≥18 years who have responded inadequately to several alternative treatments and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity
Ezogabine may be confused with ezetimibe.
Potiga may be confused with Portia
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the adverse/toxic effect of Ezogabine. Alcohol (Ethyl) may increase the serum concentration of Ezogabine. Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Ezogabine. Management: Consider increasing the ezogabine dose when adding carbamazepine. Monitor patients using the combination closely for evidence of adequate ezogabine therapy. Risk D: Consider therapy modification
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fosphenytoin-Phenytoin: May decrease the serum concentration of Ezogabine. Management: Consider increasing the ezogabine dose when adding phenytoin. Patients using this combination should be monitored closely for evidence of adequate ezogabine therapy. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
LamoTRIgine: Ezogabine may decrease the serum concentration of LamoTRIgine. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies.
Patients exposed to ezogabine during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
It is not known if ezogabine is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made to continue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Seizures; electrolytes, bilirubin, QT interval (in patients with risk factors for QT prolongation), renal and hepatic function; urologic symptoms; observe patient for excessive sedation, confusion, psychotic symptoms, and hallucinations; suicidality (eg, suicidal thoughts, depression, behavioral changes); skin discoloration (blue, or gray-blue or brown in color) around the lips, nail beds of fingers or toes, face and legs.
Ophthalmic exams (at least visual acuity testing, dilated fundus photography, and optical coherence tomography) at baseline and 6-month intervals; fluorescein angiograms, optical coherence tomography, perimetry, and electroretinograms may also be considered.
Ezogabine binds the KCNQ (Kv7.2-7.5) voltage-gated potassium channels, thereby stabilizing the channels in the open formation and enhancing the M-current. As a result, neuronal excitability is regulated and epileptiform activity is suppressed. In addition, ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.
Absorption: Rapid
Distribution: Vdss: 2 to 3 L/kg
Protein binding: Ezogabine: ~80%; N-acetyl active metabolite (NAMR): ~45%
Metabolism: Glucuronidation via UGT1A4, UGT1A1, UGT1A3, and UGT1A9 and acetylation via NAT2 to an N-acetyl active metabolite (NAMR) and other inactive metabolites (eg, N-glucuronides, N-glucoside)
Bioavailability: Oral: ~60%
Half-life elimination: Ezogabine and NAMR: 7 to 11 hours; increased by ~30% in elderly patients
Time to peak, plasma: 0.5 to 2 hours; delayed by 0.75 hours when administered with high-fat food
Excretion: Urine (~85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR); feces (~14%, 3% of total dose as unchanged drug)
Altered kidney function: The AUC was increased by ~30% in patients with mild renal impairment and doubled in patients with moderate impairment to ESRD (CrCl <50 mL/minute) relative to healthy subjects.
Hepatic function impairment: The AUC was increased by ~50% in subjects with moderate hepatic impairment and doubled in subjects with severe hepatic impairment. There was an increase of ~30% in exposure to NAMR in patients with moderate to severe hepatic impairment.
Older adult: The AUC was ~40% to 50% higher and terminal half-life was prolonged by ~30% in elderly patients compared with younger subjects.
Sex: The AUC values were ~20% higher in younger females compared with younger males and ~30% higher in elderly women compared with elderly men. The Cmax values were ~50% higher in younger females compared with younger males and ~100% higher in elderly women compared with elderly men.
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