Retigabine
Retigabine Uses, Dosage, Side Effects, Food Interaction and all others data.
Retigabine (D23129) is a close structural analog of the centrally acting analgesic flupitrine. It is a neuronal potassium channel opener being developed as a first-in-class antiepileptic drug (AED) and is currently being studied in Phase 3 trials as an adjunctive treatment for partial-onset seizures in adult patients with refractory epilepsy. FDA approved in June 10, 2011 under the name of ezogabine.
As compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Retigabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.
| Trade Name | Retigabine |
| Availability | Discontinued |
| Generic | Ezogabine |
| Ezogabine Other Names | Ezogabine, Retigabina, Retigabine |
| Related Drugs | gabapentin, clonazepam, lamotrigine, diazepam, pregabalin, Lyrica, topiramate, levetiracetam, Keppra, Topamax |
| Type | |
| Formula | C16H18FN3O2 |
| Weight | Average: 303.3314 Monoisotopic: 303.13830504 |
| Protein binding | Approximately 80% protein bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Retigabine is an antiepileptic agent used as an adjuvant treatment of partial-onset seizures.
Adjuvant treatment of partial-onset seizures.
Retigabine is also used to associated treatment for these conditions: Refractory Partial Onset Seizures
How Retigabine works
Retigabine has a novel mechanism of action that involves opening of neuronal Kv7.2-7.5 (formerly KCNQ2-5) voltage activated potassium channels. These channels (primarily Kv7.2/7.3) enable generation of the M-current, a sub-threshold potassium current that serves to stabilize the membrane potential and control neuronal excitability. In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA-A receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA-A receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically potentiates GABA-induced current in rat cortical neurons in a concentration-dependent manner. Numerous studies have demonstrated that retigabine is effective in a broad spectrum of in vivo epilepsy and seizure models.
Toxicity
Lethal Dose, acute, oral, rat = 100 mg/kg; Lethal Dose, chronic, oral, rat = 5.1 mg/kg/day, 90-day; Most common adverse effects that lead to discontinuation of therapy include dizziness and somnolence.
Food Interaction
- Take with or without food. High-fat meals alter drug absorption, but not to a clinically significant extent.
[Moderate] GENERALLY AVOID: Alcohol may increase the plasma concentrations of ezogabine.
In a study of healthy volunteers, the administration of ezogabine 200 mg in combination with ethanol 1g According to the product labeling, high-fat food does not affect the extent to which ezogabine is absorbed, but increases peak plasma concentration (Cmax) by approximately 38% and delays the time to reach peak concentration (Tmax) by 0.75 hour. Patients should be advised of the potential for increased dose-related adverse reactions of ezogabine (e.g., dizziness, somnolence, nausea, constipation, urinary retention, blurred vision, memory impairment, tremor) when taken with alcohol, and to avoid hazardous activities that require mental alertness and motor coordination until they know how the medication affects them. Retigabine can be taken with or without food.
Food does not significantly affect the bioavailability of ezogabine.
MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents.
Retigabine Disease Interaction
Moderate: suicidal tendency, alcoholism, hepatic impairment, hyperbilirubinemia, QT prolongation, renal impairment, retinal abnormalities, urinary retention
Volume of Distribution
8.7 L/kg
Elimination Route
Rapidly absorbed and distributed, with an absolute oral bioavailability of 60%. Pharmacokinetics of ezogabine suggest first-order kinetics. Tmax, single oral dose = 30-120 minutes; Time to steady state = 3 days
Half Life
Terminal half-life = 7.5 hours
Clearance
0.58 - 0.76 L/h·kg. Clearance may differ between ethnic groups with Black Americans having 20% lower clearance than Caucasian Americans.
Elimination Route
Urine (85%, 36% of total dose as unchanged drug, 18% of total dose as NAMR) and feces (14%, 3% of total dose as unchanged drug)
Innovators Monograph
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