Potiga

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Store ezogabine in a safe place so that no one else can take it accidentally or on purpose. Keep track of how many tablets are left so you will know if any are missing.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Ezogabine is used together with other medicines to control partial seizures (convulsions) in the treatment of epilepsy.

Ezogabine belongs to a class of medicines called anticonvulsants. It acts in the brain to prevent seizures. However, this medicine cannot cure epilepsy and will only work to control seizures as long as you continue to take it.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

• Tablet

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

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; or
• 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.

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

• Potiga 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. It is not possible to determine whether Potiga caused this decreased visual acuity.
• The rate of progression of retinal abnormalities and their reversibility are unknown.
• Patients who fail to show substantial clinical benefit after adequate titration should be discontinued from Potiga.
• All patients taking Potiga 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, Potiga should be discontinued unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss. 

You should not use ezogabine if you are allergic to it.

To make sure ezogabine is safe for you, tell your doctor if you have:

• kidney disease;

• liver disease;

• an enlarged prostate or urination problems;

• heart disease or a heart rhythm disorder;

• a history of depression, mental illness, or suicidal thoughts or actions;

• a personal or family history of long QT syndrome; or

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

Long-term use of ezogabine has caused a blue-colored appearance of the skin or eyes in some people. This effect was seen mainly in the lips, face, legs, fingernails, and toenails. You should have your eyes checked before you start taking ezogabine.

Ezogabine may be habit forming. Never share ezogabine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Follow your doctor's instructions about taking seizure medication if you are pregnant. Seizure control is very important during pregnancy, and having a seizure could harm both mother and baby. Do not start or stop taking this medicine without your doctor's advice, and tell your doctor right away if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of ezogabine on the baby.

It is not known whether ezogabine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using ezogabine.

Do not give this medication to anyone under 18 years old without medical advice.

Seizure Disorders

Management (in combination with other anticonvulsants) of partial-onset seizures in adults who have not responded to alternative therapies and for whom the benefits outweigh the risk of retinal abnormalities and potential decline in visual acuity.1 2 3 4 8 31 (See Ocular Effects under Cautions.)

Storage

Oral

20–25°C (may be exposed to 15–30°C).1

• Importance of providing patient with a copy of manufacturer's patient information (medication guide) when ezogabine treatment is begun and each time the drug is dispensed.1 33 Importance of patients reading the information carefully and discussing any questions with their clinician.1

• Risk of retinal abnormalities and vision loss.1 34 35 Importance of patients obtaining baseline and periodic eye examinations during therapy.1 34 35 Advise patients to promptly contact their clinician if any vision changes occur.1 34

• Risk of urinary retention, including urinary hesitation and dysuria.1 3 27 33 Advise patients of the need to maintain regular voiding3 and to seek immediate medical assistance if any symptoms of urinary retention, inability to urinate, and/or pain with urination occurs.1 In patients who cannot reliably report symptoms of urinary retention (e.g., patients with cognitive impairment), urologic consultation may be helpful.1 27

• Risk of discoloration of the nails, lips, palate, and parts of the eye.1 Advise patients to notify their clinician if any skin discoloration develops (usually reported after long-term therapy, but may occur earlier).1

• Risk of psychiatric symptoms (e.g., confusional state, disorientation, hallucinations, other psychotic symptoms); advise patients and their caregivers to notify their clinician if any such symptoms occur.1

• Risk of dizziness, somnolence, memory impairment, abnormal coordination/balance, attention disturbance, and ophthalmologic effects (e.g., diplopia, blurred vision), particularly during initiation of therapy and dosage titration.1 32 Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have become accustomed to any such effects.1 Advise patients that alcohol can increase the dose-related adverse effects of ezogabine.1 6 7

• Risk of suicidality (anticonvulsants, including ezogabine, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 10 12 Importance of patients, family members, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one's life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 10

• Advise patients not to abruptly discontinue therapy without consulting their clinician.1 Inform patients that sudden discontinuance of ezogabine can increase the risk of seizures.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of clinicians informing women about the existence of and encouraging enrollment in the NAAED Pregnancy Registry (see Pregnancy under Cautions).1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., enlarged prostate, kidney or liver disease, depression or other mood disorders, QT-interval prolongation) or family history of suicidality or bipolar disorder.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

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.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Calcifediol
• Carbamazepine
• Fosphenytoin
• Lamotrigine
• Orlistat
• Phenytoin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

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

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

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

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Check with your doctor right away if blurred vision or vision changes occur with this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may cause problems with urination. Call you doctor right away if you have trouble emptying your bladder or pain while urinating.

Using this medicine for a long time may cause your skin, nails, lips, mouth, or eyes to have a blue or brown color. Tell your doctor right away if you notice any color changes with this medicine.

Ezogabine may cause some people to be agitated, irritable, or display other abnormal behaviors, such as feeling sad or hopeless, getting upset easily, or feeling nervous, restless, or hostile. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you notice any of these adverse effects, tell your doctor right away.

Ezogabine may cause some people to become dizzy, drowsy, or have blurred vision or double vision. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert or not able to see well. If these reactions are especially bothersome, check with your doctor.

Contact your doctor right away if you have symptoms of heart rhythm problems such as feeling dizzy, feeling faint, or having a fast, pounding, or uneven heartbeat. Make sure your doctor knows if you or anyone in your family has ever had a heart rhythm problem such as QT prolongation.

Do not suddenly stop taking this medicine without checking first with your doctor. If you have been instructed to stop taking ezogabine, ask your doctor how to slowly decrease the dose. This will decrease your chance of having more seizures.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Signs, Symptoms, and Laboratory Findings

There is limited experience of overdose with Potiga. Total daily doses of Potiga over 2,500 mg were reported during clinical trials. In addition to adverse reactions seen at therapeutic doses, symptoms reported with overdose of Potiga included agitation, aggressive behavior, and irritability. There were no reported sequelae.

In an abuse potential study, cardiac arrhythmia (asystole or ventricular tachycardia) occurred in 2 volunteers within 3 hours of receiving a single 900-mg dose of Potiga. The arrhythmias spontaneously resolved and both volunteers recovered without sequelae.

Management of Overdose

There is no specific antidote for overdose with Potiga. In the event of overdose, standard medical practice for the management of any overdose should be used. An adequate airway, oxygenation, and ventilation should be ensured; monitoring of cardiac rhythm and vital sign measurement is recommended. A certified poison control center should be contacted for updated information on the management of overdose with Potiga.

Hemodialysis has been shown to reduce the plasma concentrations of ezogabine and NAMR in subjects with ESRD [see Clinical Pharmacology (12.3)].

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Applies to ezogabine: oral tablet

Ocular

Very common (10% or more): Retinal pigmentary abnormalities (up to 30%)
Common (1% to 10%): Diplopia, blurred vision
Frequency not reported: Decreased visual acuity, nystagmus
Postmarketing reports: Acquired vitelliform lesions[Ref]

Dermatologic

Very common (10% or more): Discoloration of the skin, palate, scleral, nail, conjunctiva, lip, and/or mucous membrane (up to 40%)
Uncommon (0.1% to 1%): Hyperhidrosis, skin rash
Frequency not reported: Alopecia[Ref]

Psychiatric

Common (1% to 10%): Confusional state, psychotic disorders, hallucinations, anxiety, disorientation
Frequency not reported: Euphoric mood[Ref]

Nervous system

Very common (10% or more): Dizziness (up to 23%), somnolence (up to 22%)
Common (1% to 10%): Memory impairment, tremor, vertigo, abnormal coordination, disturbance in attention, gait disturbance, aphasia, dysarthria, balance disorder, paresthesia, amnesia, myoclonus
Frequency not reported: Syncope, coma, encephalopathy[Ref]

Genitourinary

Common (1% to 10%): Urinary retention, urinary hesitation, dysuria, hematuria, chromaturia[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, constipation, dyspepsia, dry mouth
Uncommon (0.1% to 1%): Dysphasia[Ref]

Hematologic

Frequency not reported: Leukopenia, neutropenia, thrombocytopenia[Ref]

Hepatic

Common (1% to 10%): Increased liver enzymes (less than 2%)
Frequency not reported: Nephrolithiasis[Ref]

Immunologic

Common (1% to 10%): Influenza[Ref]

Metabolic

Common (1% to 10%): Increased weight, increased appetite[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Hypokinesia
Frequency not reported: Muscle spasms[Ref]

Other

Very common (10% or more): Fatigue (up to 15%)
Common (1% to 10%): Asthenia, malaise, peripheral edema[Ref]

Renal

Uncommon (0.1% to 1%): Nephrolithiasis
Frequency not reported: Renal colic[Ref]

Respiratory

Frequency not reported: Dyspnea[Ref]

Some side effects of Potiga may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.