Vd: 0.87 L/kg

Rapidly and extensively metabolized by hydrolytic first-pass metabolism to the major active metabolite eslicarbazepine and minor active metabolites (R)-licarbazepine and oxcarbazepine; active metabolites are further metabolized to inactive glucuronides.

Urine (90%; ~66% eslicarbazepine, ~33% glucuronide conjugate forms, ~10% other minor metabolites)

Eslicarbazepine: 1 to 4 hours

Adult: 13 to 20 hours; Pediatric: 10 to 16 hours

<40%

Following a single 800 mg dose, systemic exposure was increased by 62% with mild renal impairment (CrCl 50 to 80 mL/minute), 2-fold with moderate renal impairment (CrCl 30 to 49 mL/minute), and 2.5-fold with severe renal impairment (CrCl <30 mL/minute). Repeated hemodialysis removes metabolites from systemic circulation in patients with end stage renal disease.

Partial-onset seizures (epilepsy): Monotherapy or adjunctive therapy in the treatment of partial-onset seizures in adults and pediatric patients ≥4 years of age

Hypersensitivity to eslicarbazepine, oxcarbazepine, or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to carbamazepine; history of, or presence of, second- or third-degree atrioventricular block

Partial-onset seizures (epilepsy):

Monotherapy: Oral: Initial: 400 mg once daily; may initiate treatment at 800 mg once daily if seizure reduction outweighs risk of adverse reactions during initiation. Increase in weekly increments of 400 mg to 600 mg based on clinical response and tolerability. Maintenance: 800 mg to 1,600 mg once daily. Note: Consider 800 mg once daily for maintenance therapy in patients not tolerating 1,200 mg once daily.

Adjunctive therapy: Oral: Initial: 400 mg once daily; may initiate treatment at 800 mg once daily if seizure reduction outweighs risk of adverse reactions during initiation. Increase in weekly increments of 400 mg to 600 mg, based on clinical response and tolerability. Maintenance: 800 mg to 1,600 mg once daily. Note: Consider 1,600 mg once daily for maintenance therapy in patients not achieving response on 1,200 mg daily dosage.

Dosage adjustment with concomitant antiepileptic drugs (AEDs):

Adjunctive therapy:

Carbamazepine: Dose adjustment of eslicarbazepine or carbamazepine may be needed based on efficacy or tolerability.

Other enzyme-inducing antiepileptic drugs (eg, phenobarbital, phenytoin, primidone): Dosage of eslicarbazepine may need to be increased.

Oxcarbazepine: Concomitant use is not recommended.

Partial-onset seizures (epilepsy) (monotherapy or adjunctive therapy): Children ≥4 years of age and Adolescents: Oral:

11 to 21 kg: Initial: 200 mg once daily; increase in weekly increments of no more than 200 mg, based on clinical response and tolerability. Maintenance: 400 to 600 mg once daily. Maximum: 600 mg/day.

22 to 31 kg: Initial: 300 mg once daily; increase in weekly increments of no more than 300 mg, based on clinical response and tolerability. Maintenance: 500 to 800 mg once daily. Maximum: 800 mg/day.

32 to 38 kg: Initial: 300 mg once daily; increase in weekly increments of no more than 300 mg, based on clinical response and tolerability. Maintenance: 600 to 900 mg once daily. Maximum: 900 mg/day.

>38 kg: Initial: 400 mg once daily; increase in weekly increments of no more than 400 mg, based on clinical response and tolerability. Maintenance: 800 to 1,200 mg once daily. Maximum: 1,200 mg/day.

Mild impairment (CrCl ≥50 to 80 mL/minute): There are no dosage adjustments provided in the manufacturer's labeling; systemic exposure increased 62% following a single 800 mg dose.

Moderate to severe renal impairment (CrCl <50 mL/minute): Reduce initial, titration, and maintenance dosage by 50%; may base titration and maintenance dosage adjustments on clinical response.

End-stage renal disease (ESRD) undergoing hemodialysis: There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Repeated dialysis removes metabolites.

Mild to moderate hepatic impairment: No dosage adjustment necessary.

Severe hepatic impairment: Use is not recommended (has not been studied).

Administer with or without food; tablets may be swallowed whole or crushed.

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

CarBAMazepine: May enhance the adverse/toxic effect of Eslicarbazepine. CarBAMazepine may decrease the serum concentration of Eslicarbazepine. Monitor therapy

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical).Monitor therapy

Estrogen Derivatives (Contraceptive): Eslicarbazepine may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Alternative non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Fosphenytoin: May decrease the serum concentration of Eslicarbazepine. (based on studies with phenytoin) Eslicarbazepine may increase the serum concentration of Fosphenytoin. (based on studies with phenytoin) Monitor therapy

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating concomitant therapy with moderate CYP3A4 inducers. Increase guanfacine dose gradually over 1-2 weeks if moderate CYP3A4 inducer therapy is just beginning. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone.Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil.Monitor therapy

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine.Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine.Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

OXcarbazepine: Eslicarbazepine may enhance the adverse/toxic effect of OXcarbazepine. Avoid combination

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers.Consider therapy modification

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

PHENobarbital: May decrease the serum concentration of Eslicarbazepine. Monitor therapy

Phenytoin: May decrease the serum concentration of Eslicarbazepine. Eslicarbazepine may increase the serum concentration of Phenytoin. Monitor therapy

Primidone: May decrease the serum concentration of Eslicarbazepine. (based on studies with phenobarbital) Monitor therapy

Progestins (Contraceptive): Eslicarbazepine may decrease the serum concentration of Progestins (Contraceptive). Management: Alternative, non-hormonal means of birth control should be considered for women of child-bearing potential. Consider therapy modification

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

Rosuvastatin: Eslicarbazepine may decrease the serum concentration of Rosuvastatin. Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Simvastatin: Eslicarbazepine may decrease the serum concentration of Simvastatin. Monitor therapy

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Warfarin: Eslicarbazepine may decrease the serum concentration of Warfarin. Specifically, S-warfarin serum concentrations may be decreased. Monitor therapy

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

>10%:

Central nervous system: Dizziness (20% to 28%), drowsiness (11% to 28%), headache (13% to 15%)

Gastrointestinal: Nausea (10% to 16%)

Ophthalmic: Diplopia (9% to 11%)

1% to 10%:

Cardiovascular: Hypertension (2%), peripheral edema (2%)

Central nervous system: Fatigue (7%), cognitive dysfunction (4% to 7%), ataxia (4% to 6%), vertigo (2% to 6%), depression (3%), equilibrium disturbance (3%), falling (3%), abnormal gait (2%), insomnia (2%), dysarthria (1% to 2%), memory impairment (1% to 2%)

Dermatologic: Skin rash (3%)

Endocrine & metabolic: Hyponatremia (serum sodium <125 mEq/L: 1% to 2%)

Gastrointestinal: Vomiting (6% to 10%), diarrhea (4%), abdominal pain (2%), constipation (2%), gastritis (2%)

Genitourinary: Urinary tract infection (2%)

Neuromuscular & skeletal: Tremor (2% to 4%), weakness (3%)

Ophthalmic: Blurred vision (5% to 6%), decreased visual acuity (2%), nystagmus (1% to 2%)

Respiratory: Cough (2%)

Frequency not defined:

Endocrine & metabolic: Hypercholesterolemia, hypochloremia (concurrent with hyponatremia), increased LDL cholesterol, increased serum triglycerides

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin

Neuromuscular & skeletal: Increased creatine phosphokinase

<1% (Limited to important or life-threatening): Agranulocytosis, anaphylaxis, angioedema, decreased T3 level, decreased T4 (free and total), DRESS syndrome, increased serum bilirubin (>2 x ULN), increased serum transaminases (>3 x ULN), leukopenia, megaloblastic anemia, pancytopenia, prolongation P-R interval on ECG (mild [Vas-Da-Silva 2012]), severe dermatological reaction, SIADH, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis

Concerns related to adverse effects:

• CNS effects: Use has been associated with dose-dependent CNS-related adverse events, most significant of these were cognitive symptoms (eg, memory impairment, disturbance in attention, amnesia, confusional state, aphasia, speech disorder, slowness of thought, disorientation, psychomotor retardation), somnolence or fatigue, dizziness and coordination abnormalities (eg, ataxia, vertigo, balance disorder, gait disturbance, nystagmus, abnormal coordination), and visual changes (eg, diplopia, blurred vision, impaired vision). There was an increased risk of visual changes and dizziness and coordination abnormalities during the titration period, in patients >60 years of age, and with concomitant carbamazepine use; consider dosage modifications in patients using eslicarbazepine and carbamazepine concomitantly. Caution patients about performing tasks which require mental alertness (eg, operating machinery or driving).

• Dermatologic reactions: Potentially serious, sometimes fatal, dermatologic reactions including Stevens-Johnson syndrome (SJS) have been reported; monitor for signs and symptoms of skin reactions; discontinuation and conversion to alternate therapy may be required. Avoid use in patients with prior dermatologic reaction with either oxcarbazepine or eslicarbazepine.

• Hematologic effects: Cases of pancytopenia, agranulocytosis, and leukopenia have been reported; consider discontinuing eslicarbazepine if these hematologic abnormalities develop.

• Hepatic effects: Hepatic effects ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases of concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported. Perform baseline liver laboratory tests. Discontinue in patients with jaundice or other evidence of significant liver injury.

• Hypersensitivity reactions: Rare cases of anaphylaxis and angioedema have been reported. Permanently discontinue should symptoms occur. Avoid use in patients with a prior anaphylactic-type reaction with either oxcarbazepine or eslicarbazepine.

• Hyponatremia: Clinically significant hyponatremia (serum sodium <125 mmol/L) and concurrent hypochloremia may develop during use. In controlled trials, effects were dose-related, appeared within the first 8 weeks of treatment (as early as after 3 days), and resolved without additional treatment after eslicarbazepine was discontinued. Consider monitoring serum sodium and chloride levels during maintenance treatment, especially in patients at risk for hyponatremia and if symptoms of hyponatremia develop. Depending on the severity of hyponatremia, the dose of eslicarbazepine may need to be reduced or discontinued.

• Multiorgan hypersensitivity reactions: Potentially serious, sometimes fatal drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, have been reported. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Evaluate immediately if signs or symptoms are present. Discontinuation and conversion to alternate therapy may be required. Avoid use in patients with a prior DRESS reaction with either oxcarbazepine or eslicarbazepine.

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; patients should be instructed to notify healthcare provider immediately if symptoms occur.

• Thyroid function: Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed; changes were not associated with other abnormal thyroid function tests suggesting hypothyroidism.

Disease-related concerns:

• Renal impairment: Clearance is decreased in patients with impaired renal function; dosage adjustment is necessary in patients with CrCl <50 mL/minute.

• Hepatic impairment: Avoid use in patients with severe hepatic impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Seizure frequency; liver enzymes (baseline); serum sodium and chloride as deemed necessary during maintenance treatment, particularly in patients receiving other medications known to decrease sodium levels or if symptoms of hyponatremia develop; symptoms of CNS depression (dizziness, disturbance in gait and coordination, somnolence); visual changes; hypersensitivity reactions. Monitor for suicidality (eg, suicidal thoughts, depression, behavioral changes). For adjunctive therapy, serum levels of concomitant antiepileptic drugs during titration as necessary.

DELETE

Adverse events have been observed in animal reproduction studies. Eslicarbazepine may decrease plasma concentrations of hormonal contraceptives; additional or alternative nonhormonal contraceptives are recommended in women of reproductive potential.

Patients exposed to eslicarbazepine during pregnancy are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at http://www.aedpregnancyregistry.org.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, nausea, vomiting, fatigue, or tremors. Have patient report immediately to prescriber signs of infection, signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), swollen glands, shortness of breath, excessive weight gain, swelling of arms or legs, angina, severe dizziness, passing out, severe muscle pain, severe muscle weakness, severe loss of strength and energy, vision changes, seizures, bruising, bleeding, chills, involuntary eye movements, difficulty walking, agitation, irritability, panic attacks, mood changes, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.