Aptiom

Eslicarbazepine is used in combination with other medications to control focal (partial) seizures (seizures that involve only one part of the brain). Eslicarbazepine is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the brain.

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.

Anticonvulsant; a dibenz[b,f]azepine-5-carboxamide derivative.1 4 6 7 9 Eslicarbazepine acetate is a prodrug that is metabolized to eslicarbazepine (S-licarbazepine), the major active metabolite of oxcarbazepine.1 4 6 7 9 27

General

• Avoid abrupt discontinuance; withdraw gradually to minimize potential for increased seizure frequency and status epilepticus.1 (See Discontinuance of Therapy under Cautions.)

• Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 10 11 12 (See Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer orally once daily with or without food.1

Tablets may be swallowed whole or crushed.1

Dosage

Available as eslicarbazepine acetate; dosage expressed in terms of the acetate salt.1

Adults

Initially, 400 mg once daily.1

Increase to recommended maintenance dosage of 800 mg once daily after 1 week.1

May increase to 1.2 g once daily only if patient tolerates 800 mg once daily for at least 1 week.1 In clinical studies, the 1.2-g daily dosage was associated with increased adverse effects.1 2

In some patients, may initiate therapy with 800 mg once daily if need for additional seizure reduction outweighs risk of increased adverse effects during initiation of therapy.1 4

Concurrent Use of Other Anticonvulsants

Oxcarbazepine: Because eslicarbazepine is the S-enantiomer of the major metabolite of oxcarbazepine, avoid concurrent use.1 6 7 8

Carbamazepine: Dosages of eslicarbazepine acetate and/or carbamazepine may require adjustment based on efficacy and tolerability (see Specific Drugs under Interactions).1

Other CYP-inducing anticonvulsants (e.g., phenobarbital, phenytoin, primidone): Higher dosages of eslicarbazepine acetate may be necessary (see Specific Drugs under Interactions).1

Prescribing Limits

Adults

1.2 g once daily.1

Special Populations

Hepatic Impairment

Mild to moderate hepatic impairment: No dosage adjustment necessary.1

Severe hepatic impairment: Not studied; use not recommended.1

Renal Impairment

Mild renal impairment: No dosage adjustment necessary.1

Moderate to severe renal impairment (Clcr <50 mL/minute): Initially, 200 mg once daily.1 After 2 weeks, increase dosage to recommended maintenance dosage of 400 mg once daily.1 Some patients may benefit from the maximum recommended maintenance dosage of 600 mg once daily.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Routine dosage adjustment based on age not necessary; however, dosage adjustment necessary if Clcr <50 mL/minute.1 (See Geriatric Use under Cautions.)

Gender or Race

Dosage adjustment not required.1

Moderate inhibitor of CYP2C19; may induce CYP3A4.1 8

Does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2D6, 2E1, 3A4, nor to induce CYP1A2 or phase II hepatic enzymes involved in glucuronidation or sulfation.1 8 Mild activation of UGT1A1-mediated glucuronidation observed in vitro.1

Autoinduction of metabolism not observed.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions (e.g., decreased eslicarbazepine exposure) with inducers of CYP3A4; higher dosages of eslicarbazepine acetate may be necessary.1 8

Potential pharmacokinetic interactions (e.g., decreased substrate concentrations) with concomitant use of CYP3A4 substrates; higher dosages of the CYP3A4 substrate may be necessary.1 27

Potential pharmacokinetic interactions (e.g., increased substrate concentrations) with concomitant use of CYP2C19 substrates.1 27

Drugs associated with Hyponatremia

Possible increased risk of hyponatremia during concomitant use of other drugs associated with hyponatremia; consider monitoring sodium and chloride concentrations during concurrent therapy.1 25

Specific Drugs

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 therapy is initiated and each time the drug is dispensed.1

• Importance of taking only as prescribed.1

• Risk of suicidality (anticonvulsants, including eslicarbazepine acetate, 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

• Importance of informing patients and caregivers about the risk of serious, potentially fatal skin reactions.1 Importance of informing patients about the signs and symptoms that may signal a serious skin reaction and instructing patients to immediately consult with their clinician if a skin reaction occurs during treatment.1

• Risk of drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity.1 Importance of advising patients that a fever associated with signs of other organ system involvement (e.g., rash, lymphadenopathy, hepatic dysfunction) may be drug-related and should be reported to their clinician immediately.1

• Importance of advising patients of life-threatening symptoms suggesting anaphylaxis or angioedema (e.g., swelling of the face, eyes, tongue; difficulty swallowing or breathing) that may occur.1 Importance of instructing patients to immediately report such symptoms to their clinician.1

• Importance of advising patients that eslicarbazepine acetate can cause hyponatremia, particularly in patients receiving other drugs that can lower serum sodium concentrations.1 Patients should be advised to promptly contact their clinician if they develop any symptoms of hyponatremia (e.g., nausea, tiredness, lack of energy, irritability, confusion, muscle weakness or spasms, increase in seizure frequency or severity).1

• Importance of advising patients of risk of adverse neurologic effects such as dizziness, gait disturbance, somnolence, fatigue, cognitive dysfunction, and visual disturbances.1 These effects are more likely to occur during the dosage titration phase (compared with the maintenance phase).1 Importance of advising patients not to drive, operate machinery, or engage in other hazardous activities until the effects of drug therapy are known.1

• Importance of advising patients not to discontinue eslicarbazepine acetate therapy without consulting with their clinician.1 The drug should be gradually withdrawn to minimize the risk of increased seizure frequency and status epilepticus.1

• Importance of informing women that eslicarbazepine acetate can substantially decrease the effectiveness of hormonal contraceptives.1 8 Women of childbearing potential should be advised to use additional or alternative nonhormonal forms of contraception during therapy and for at least one menstrual cycle after discontinuance or until otherwise instructed by their clinician.1 8

• 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 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., kidney or liver disease) or history of suicidality, depression, or mood 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 eslicarbazepine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of eslicarbazepine 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 kidney problems, which may require caution and an adjustment in the dose for patients receiving eslicarbazepine.

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.

• Amitriptyline
• Calcifediol
• Carbamazepine
• Carisoprodol
• Ceritinib
• Cilostazol
• Citalopram
• Clobazam
• Clomipramine
• Cobicistat
• Cyclophosphamide
• Diazepam
• Dolutegravir
• Doxepin
• Escitalopram
• Esomeprazole
• Fosphenytoin
• Idelalisib
• Lacosamide
• Lansoprazole
• Mephenytoin
• Meprobamate
• Nelfinavir
• Nilotinib
• Olaparib
• Omeprazole
• Orlistat
• Ospemifene
• Palbociclib
• Pantoprazole
• Phenobarbital
• Phenytoin
• Piperaquine
• Primidone
• Progesterone
• Propranolol
• Rabeprazole
• Rosuvastatin
• Simvastatin
• Voriconazole
• Vortioxetine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ethinyl Estradiol
• Levonorgestrel
• Warfarin

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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

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:

• Depression, history of or
• Hyponatremia (low sodium in the blood) or
• Mental illness, history of—Use with caution. May make these conditions worse.

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

Aptiom tablets are available in the following shapes and color (Table 2) with respective one-sided engraving:

Aptiom is usually given once per day. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take this medicine with or without food. The Aptiom tablet may be crushed or swallowed whole.

Aptiom can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using eslicarbazepine.

Do not stop using this medicine suddenly, even if you feel fine. Stopping suddenly may cause increased seizures. Follow your doctor's instructions about tapering your dose.

Store Aptiom at room temperature away from moisture and heat.

Aptiom may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you.