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These highlights do not include all the information needed to use POTIGA
safely and effectively. See full prescribing information for POTIGA.
POTIGA (ezogabine) Tablets Initial U.S. Approval: 2011
Mechanism of Action
The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. In vitro studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ (Kv7.2 to 7.5) family of ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. In vitro studies suggest that ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.
Results of a mass balance study suggest that renal excretion is the major route of elimination for ezogabine and NAMR. About 85% of the dose was recovered in the urine, with the unchanged parent drug and NAMR accounting for 36% and 18% of the administered dose, respectively, and the total N-glucuronides of ezogabine and NAMR accounting for 24% of the administered dose. Approximately 14% of the radioactivity was recovered in the feces, with unchanged ezogabine accounting for 3% of the total dose. Average total recovery in both urine and feces within 240 hours after dosing is approximately 98%.
Ezogabine and its N-acetyl metabolite have similar elimination half-lives (t 1/2) of 7 to 11 hours. The clearance of ezogabine following intravenous dosing was approximately 0.4 to 0.6 L/hr/kg. Ezogabine is actively secreted into the urine.
INDICATIONS AND USAGE
POTIGA is a potassium channel opener indicated as adjunctive treatment of partial-onset seizures in patients aged 18 years and older.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. Pregnancy registry available.
Pediatric use: Safety and effectiveness in patients under 18 years of age have not been established.
Ezogabine plasma levels may be reduced by concomitant administration of phenytoin or carbamazepine. An increase in dosage of POTIGA should be considered when adding phenytoin or carbamazepine.
N-acetyl metabolite of ezogabine may inhibit renal clearance of digoxin, a P-glycoprotein substrate. Monitor digoxin levels.
WARNINGS AND PRECAUTIONS
Urinary retention: Patients should be carefully monitored for urologic symptoms.
Neuropsychiatric symptoms: Monitor for confusional state, psychotic
symptoms, and hallucinations.
Dizziness and somnolence: Monitor for dizziness and somnolence.
QT prolongation: QT interval should be monitored in patients taking concomitant medications known to increase the QT interval or with certain heart conditions.
Suicidal behavior and ideation: Monitor for suicidal thoughts or behaviors.
|The most common adverse reactions (incidence 4% and approximately twice placebo) are dizziness, somnolence, fatigue, confusional state, vertigo, tremor, abnormal coordination, diplopia, disturbance in attention, memory impairment, asthenia, blurred vision, gait disturbance, aphasia, dysarthria, and balance disorder.|
DOSAGE AND ADMINISTRATION
•Administer in 3 divided doses daily, with or without food.
•The initial dosage should be 100 mg 3 times daily (300 mg per day) for 1 week.
•Titrate to maintenance dosage by increasing the dosage at weekly intervals by no more than 150 mg per day.
•Optimize effective dosage between 200 mg 3 times daily (600 mg per day) to 400 mg 3 times daily (1,200 mg per day).
In controlled clinical trials, 400 mg 3 times daily (1,200 mg per day) showed limited improvement compared to 300 mg 3 times daily (900 mg per day) with an increase in adverse reactions and discontinuations.
•When discontinuing POTIGA, reduce the dosage gradually over a period of at least 3 weeks.
•Dosing adjustments are required for geriatric patients and patients with moderate to severe renal or hepatic impairment
The initial dosage should be 100 mg 3 times daily (300 mg per day). The dosage should be increased gradually at weekly intervals by no more than 50 mg 3 times daily (increase in the daily dose of no more than 150 mg per day) up to a maintenance dosage of 200 to 400 mg 3 times daily (600 to 1,200 mg per day), based on individual patient response and tolerability.
This information is summarized in Table 1 under General Dosing. In the controlled clinical trials, 400 mg 3 times daily showed limited evidence of additional improvement in seizure reduction, but an increase in adverse events and discontinuations, compared to the 300 mg 3 times daily dosage. The safety and efficacy of doses greater than 400 mg 3 times daily (1,200 mg per day) have not been examined in controlled trials.
No adjustment in dosage is required for patients with mild renal or hepatic impairment. Dosage adjustment is required in patients with moderate and greater renal or hepatic impairment.
POTIGA should be given orally in 3 equally divided doses daily, with or without food.
POTIGA Tablets should be swallowed whole.
If POTIGA is discontinued, the dosage should be gradually reduced over a period of at least 3 weeks, unless safety concerns require abrupt withdrawal.
HOW SUPPLIED/STORAGE AND HANDLING
POTIGA is supplied as film-coated immediate-release tablets for oral administration containing 50, 200, 300, or 400 mg of ezogabine in the following packs:
50-mg Tablets: purple, round, film-coated tablets debossed with “RTG 50” on one side in bottles of 90 (NDC 0173-0810-59).
200-mg Tablets: yellow, oblong, film-coated tablets debossed with “RTG-200” on one side in bottles of 90 (NDC 0173-0812-59).
300-mg Tablets: green, oblong, film-coated tablets debossed with “RTG-300” on one side in bottles of 90 (NDC 0173-0813-59).
400-mg Tablets: purple, oblong, film-coated tablets debossed with “RTG-400” on one side in bottles of 90 (NDC 0173-0814-59).
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature.]
Package Insert data:
POTIGA is a trademark of Valeant Pharmaceuticals North America.
Manufactured by Catalent Pharma Solutions Somerset, NJ 08873
GlaxoSmithKline Research Triangle Park, NC 27709
©2011, GlaxoSmithKline. All rights reserved.