Ezogabine is an anti-epileptic drug, also called an anticonvulsant. Ezogabine is used to treat partial-onset seizures in adults.

Ezogabine can cause abnormal changes in your retina (the membrane layer inside your eye that helps produce vision). These changes may cause vision changes that could be permanent.Your vision will need to be checked before you start taking ezogabine, and every 6 months while you are taking it.

Excerpt from Healthwise:
https://www.cigna.com/individuals-families/health-wellness/hw/medications/ezogabine-d07769a1

This medication is used in combination with other medications to treat certain types of seizures (focal seizures). Because of the risk of vision changes, ezogabine should only be used when other medications have failed to control seizures. It works by reducing the spread of seizure activity in the brain. Ezogabine belongs to a class of drugs known as anticonvulsants. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. This medication may sometimes cause addiction.

Excerpt from Webmd:
https://www.webmd.com/drugs/2/drug-160537/potiga-oral/details

Ezogabine, which is known as retigabine in Europe, is a unique anticonvulsant used largely as an adjunctive agent in the treatment of partial seizures.

Ezogabine is an anticonvulsant with a unique mechanism of action, decreasing excitability and seizure activity by opening voltage-gated potassium channels in the brain. Ezogabine has been shown to be effective both as monotherapy and in combination with other anticonvulsants for partial seizures. Ezogabine was approved for use in the United States in 2011 and current indications are as adjunctive therapy for partial seizures. Ezogabine is available in tablets of 50, 200, 300 and 400 mg under the brand name Potiga in the United States and Trobalt in Europe and elsewhere.

Long term therapy has been associated with urinary retention and blue discoloration of the skin, lips, sclera and retina. Rare, but potentially severe adverse events include psychiatric symptoms such as confusion and hallucination and decrease in visual acuity as a result of retinal pigmentation.

Liver:
Therapy with ezogabine has not been associated with serum aminotransferase elevations, and clinically apparent liver injury from ezogabine has yet to be reported and must be rare, if it occurs at all.

Ezogabine Hepatotoxicity:
Limited data are available on the hepatotoxicity of ezogabine. In clinical trials, therapy with ezogabine was not associated with an increased frequency of serum aminotransferase elevations as compared to placebo treatment, and there were no instances of clinically apparent liver injury. No individual case reports of ezogabine hepatotoxicity have been published since its more wide spread clinical availability. Thus, clinically apparent liver injury due to ezogabine must be rare, if it occurs at all.

E Likelihood score: E (unlikely cause of clinically apparent liver injury).

Ezogabine Overview:
https://www.ncbi.nlm.nih.gov/books/NBK548304/

Ezogabine is a potassium channel opener indicated as adjunctive treatment of partial-onset seizures in patients aged 18 years and older 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 activates voltage-gated potassium channels. This leads to inhibition of hyperexcitability activity in the central nervous system (CNS). This ability to enhance the potassium channel allows seizure frequency to be reduced.

Ezogabine (Potiga) National Drug Monograph (PDF 10 pages):
https://www.pbm.va.gov/PBM/clinicalguidance/drugmonographs/Ezogabine_POTIGA_Monograph.pdf

This drug, Potiga or ezogabine, is no longer available in the United States

This drug is important because it prevents seizures in a new way different from currently existing anti-seizure medications. It is used to treat Temporal Lobe Epilepsy, Focal Impaired Awareness or Complex Partial Seizures, Refractory Seizures, Secondarily Generalized Seizures or Bilateral Tonic Clonic Seizures, Focal Aware or Simple Partial Seizures.

Most people swallow the tablets whole to avoid a bitter taste. People who cannot swallow the tablet may be able to crush the tablet and mix it with food. It is OK to take Potiga either with food or without food, but it is a good idea to take it the same way every time. Taking Potiga with food does not change how much Potiga your body absorbs, but it does slow down the absorption a bit.

In some rare cases some people taking the drug have reported bluish discoloration of the skin and nails. In addition, some individuals have reported visual loss and changes. Please talk to your doctor if any of these problems are seen so these can be watched over time.

Excerpt from epilepsy.com:
https://www.epilepsy.com/medications/ezogabine

Ezogabine (U.S. adopted name) or retigabine (international nonproprietary name) is one of a family of aminopyrroles with anticonvulsant activity. It is used as an adjunctive treatment for partial epilepsies in treatment-experienced adult patients. The drug was approved by the European Medicines Agency under the trade name Trobalt and by the United States Food and Drug Administration (FDA), under the trade name Potiga. 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. This mechanism of action is unique among antiepileptic drugs, and may hold promise for the treatment of other neurologic conditions, including migraine, tinnitus and neuropathic pain. In vitro studies suggest that ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.

Ezogabine:
https://drugs.ncats.io/drug/12G01I6BBU

THURSDAY, Nov. 1, 2018 (HealthDay News) - A drug used to control seizures may be a potent weapon against depression in patients who don't find relief with antidepressants, a small pilot study suggests. Some of the 18 patients taking ezogabine (Potiga) experienced a 45 percent reduction in depression and an increase in their ability to feel pleasure, as well as an increase in resilience and the capacity to recover from extremes of trauma and stress, the researchers reported. "This drug might be relevant for patients who don't do well with conventional antidepressants,"

Ezogabine was approved in 2011 by the U.S. Food and Drug Administration as an anti-seizure medication. Shortly after its approval, concerns were raised about the drug's effect on the retina and the possibility of it causing blindness. The FDA ordered the drug's maker, GlaxoSmithKline, to do further safety studies. After reviewing those studies, the FDA ruled in 2015 that the drug did not appear to affect vision. Still, the company withdrew ezogabine from the U.S. market in 2017, citing poor sales. Even so, psychiatrists noted that if the drug proves effective against depression in larger studies, other drugs that target this area of the brain could be developed.

Ezogabine works by increasing the activity of the area in the brain that controls potassium. Murrough explained animal studies have shown that depression can reduce the activity of this potassium channel and that ezogabine can increase its activity, thus relieving depression.

We need to find newer ways to treat depression," and ezogabine might be one of these new approaches. "This study doesn't change treatment - yet," he added. "At least this is preliminary evidence that this potassium channel target might be another avenue for treatment."

Excerpt from Webmd:
https://www.webmd.com/depression/news/20181101/anti-seizure-drug-may-help-against-depression

This medicine can cause certain eye problems. These eye problems may lead to lasting loss of eyesight. This medicine is only for use if other drugs have not worked. Eye exams will be done before starting ezogabine and during treatment to watch for these eye problems. Call your doctor right away if you have any change in eyesight. Talk with your doctor to be sure that the benefits of ezogabine are more than the risks.

What are some things I need to know or do while I take Ezogabine?
Tell all of your health care providers that you take ezogabine. This includes your doctors, nurses, pharmacists, and dentists. This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take ezogabine. Avoid driving and doing other tasks or actions that call for you to be alert until you see how ezogabine affects you. Follow laws about driving with a seizure problem. Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.

This medicine can cause a change in color of your skin, nails, lips, roof of your mouth, and parts of the eye. The changes in color may be blue, grey-blue, or brown. Most of the time, this has happened after at least 2 years of using ezogabine but it may happen before then. It is not known if the change in color will go away after stopping ezogabine. Talk with your doctor if this happens.

If you are 65 or older, use ezogabine with care. You could have more side effects. Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using ezogabine while you are pregnant.

Interactions:

Drug Interactions (414) Alcohol/Food Interactions (1) Disease Interactions (8)

What other drugs will affect Ezogabine?

A total of 414 drugs are known to interact with Ezogabine.

• 60 major drug interactions
• 350 moderate drug interactions
• 4 minor drug interactions

Ezogabine Drug Information:
https://www.drugs.com/cdi/ezogabine.html

Potiga (ezogabine tablets)

Side Effects:
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
RxList
Potiga (ezogabine tablets): https://www.rxlist.com/potiga-drug/patient-images-side-effects.htm
Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, depression, anxiety, panic attacks, or if you feel agitated, hostile, aggressive, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.
Call your doctor at once if you have: blurred vision, double vision, or any other changes in your vision painful or difficult urination little or no urination trouble emptying your bladder confusion, hallucinations, unusual thoughts or behavior
Common side effects may include: dizziness, spinning sensation weakness, loss of balance or coordination drowsiness, tired feeling memory problems, trouble concentrating tremors problems with speech or walking
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Pediatric:
Appropriate studies have not been performed on the relationship of age to the effects of ezogabine in the pediatric population.

Safety and efficacy have not been established.

Geriatric:
Although appropriate studies on the relationship of age to the effects of ezogabine have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related prostate and kidney problems, which may require caution and an adjustment in the dose for patients receiving ezogabine.

Other Interactions:

• Ethanol

Other Medical Problems:
Make sure you tell your doctor if you have any other medical problems, especially:

• Congestive heart failure
• Hypokalemia (low potassium in the blood)
• Hypomagnesemia (low magnesium in the blood) - Use with caution. May cause side effects to become worse

• Depression
• Hallucinations
• Heart rhythm problems (eg, QT prolongation)
• Mood disorder
• Urinary retention (urinating problem) - Use with caution. May make these conditions worse

• Kidney disease
• Liver disease - Use with caution. The effects may be increased because of slower removal of the medicine from the body

Ezogabine (Oral Route) (Potiga):
https://www.mayoclinic.org/drugs-supplements/ezogabine-oral-route/description/drg-20075057

Breastfeeding:

Summary of Use During Lactation:
Because no information is available on use of ezogabine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. If ezogabine is required by the mother, it is not necessarily a reason to discontinue breastfeeding, but monitor the infant for drowsiness, agitation, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of drugs.

Alternate Drugs to Consider:

• (Seizure Disorder) Carbamazepine
• Divalproex
• Gabapentin
• Lamotrigine
• Oxcarbazepine
• Phenytoin
• Valproic Acid

Ezogabine Drug Levels and Effects:
https://www.ncbi.nlm.nih.gov/books/NBK500878/

Potiga (ezogabine) (Rx)

Black Box Warnings:
Potiga (ezogabine) (Rx): https://reference.medscape.com/drug/potiga-ezogabine-999664
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 Some patients with retinal abnormalities have been found to have abnormal visual acuity; unknown if ezogabine caused this vision loss Rate of progression of retinal abnormalities and their reversibility are unknown; about 33% of patients who had eye examinations performed after 4 yr of treatment were found to have retinal pigmentary abnormalities; an earlier onset cannot be ruled out Discontinue if patient fails to show substantial clinical benefit after adequate titration All patients should have baseline and periodic (every 6 months) systematic visual monitoring by an ophthalmic professional; testing should include visual acuity and dilated fundus photography If retinal pigmentary abnormalities or vision changes are detected, discontinue ezogabine unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss

FDA Potiga Medication Guide (PDF 6 pages):
https://www.fda.gov/media/80840/download

Estazolam Medication Guide (PDF 4 pages):
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022345s001lbl.pdf

Potiga Package Insert (PDF 33 pages):
https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Potiga/pdf/POTIGA-PI-MG.PDF

European Medicines Agency Trobalt (PDF 119 pages):
https://www.ema.europa.eu/en/documents/product-information/trobalt-epar-product-information_en.pdf

Potiga Medication Guide (PDF 4 pages):
https://www.pdr.net/pdrcontent/PDRe_201409110948/mg/pdf/10185.PDF

Potiga Drug Label Information:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c60979b-489d-4e7b-8893-468ae00c44bb&audience=consumer

Australian Public Assessment Report for Retigabine (PDF 61 pages):
https://www.tga.gov.au/sites/default/files/auspar-retigabine-131017.pdf

Electronic Medicines Compendium Trobalt Tablets Package Leaflet:
https://www.medicines.org.uk/emc/files/pil.4588.pdf

Retigabine:
Calms the excitability of nerve cells that cause seizures. It appears to be free of drug interactions with most commonly used anticonvulsants. Retigabine is quickly absorbed, and reaches maximum plasma concentrations between half an hour and 2 hours after a single oral dose. It has a moderately high oral bioavailability (50 - 60%), a high volume of distribution (6.2 L/kg), and a terminal half-life of 8 to 11 hours. Retigabine requires thrice-daily dosing due to its short half-life. Retigabine is metabolized in the liver and its metabolites are excreted almost completely (84%) by the kidneys.

Retigabine was approved in 2011 and production was discontinued in 2017 "poor sales"