Drug information of Eslicarbazepine acetate

Eslicarbazepine acetate

Drug group: Anticonvulsants

Eslicarbazepine acetate (ESL) is an anticonvulsant medication approved as an adjunctive therapy for partial-onset seizures that are not adequately controlled with conventional therapy. Eslicarbazepine acetate is a prodrug that is rapidly converted to eslicarbazepine, the primary active metabolite in the body

:Dosage Forms & Strengths
Tablet: 200 mg, 400 mg. 600 mg and 800 mg

Mechanism of effect

Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity

Pharmacodynamic

Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval

Pharmacokinetics

:Absorption
Bioavailability: >90%
Peak plasma concentration: 1-4 hr as eslicarbazepine that is the major metabolite of prodrug

:Distribution
Protein bound: <40%
Vd: 61 L

:Metabolism
Rapidly and extensively metabolized to its major active metabolite (eslicarbazepine) by hydrolytic first-pass metabolism
Moderate CYP2C19 inhibitor; no apparent autoinduction

:Elimination
Half-life: 13-20 hr

:Excretion
More than 90% in urine; two-thirds as unchanged form and one-third as glucuronide conjugate

Dosage

:Initial
400mg PO qDay
For some patients, treatment may be initiated at 800 mg qDay if the need for additional seizure reduction outweighs an increased risk of adverse reactions during initiation

:Titration and Maintenance
Increase dose by weekly increments of 400-600 mg, based on clinical response and tolerability
Recommended maintenance dose is 800-1600 mg once daily
Monotherapy: Consider 800 mg/day maintenance dose in patients unable to tolerate 1200 mg/day
Adjunctive therapy: 1600 mg/day should be considered in patients who did not achieve a satisfactory response with 1200 mg/day

:Moderate to severe renal impairment
Reduce the initial, titration, and maintenance doses by 50%; may adjust titration and maintenance doses according to clinical response

:Dosing Considerations
When discontinuing eslicarbazepine acetate, gradually reduce dose and avoid abrupt discontinuation in order to minimize risk of increased seizure frequency and status epilepticus

Alerts

See FDA warning on potential suicidal behavior; monitor patients for notable changes in behavior that might be associated with suicidal thoughts or depression (notify health-care provider immediately if symptoms occur)

Antiepileptic drugs (AEDs), including eslicarbazepine, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication

Serious dermatologic reactions reported, including Stevens-Johnson syndrome (SJS); serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and SJS, have been reported in patients using oxcarbazepine or carbamazepine which are chemically related

Drug reaction with eosinophilia and systemic symptoms (DRESS) reported; DRESS may be fatal or life-threatening, and although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection

Clinically significant hyponatremia (sodium <125 mEq/L); consider monitoring serum sodium and chloride levels during maintenance treatment, particularly in patients receiving other medications known to decrease serum sodium levels, and perform in patients exhibiting symptoms of hyponatremia develop (eg, nausea/vomiting, malaise, headache, lethargy, confusion, irritability, muscle weakness/spasms, obtundation, or increase in seizure frequency or severity)

Anaphylactic reactions and angioedema: Monitor for breathing difficulties or swelling; discontinue if another cause cannot be established

Hyponatremia: Monitor sodium levels in patients at risk or patients experiencing hyponatremia symptoms

Discontinuing: Withdraw gradually to minimize risk of increased seizure frequency and status epilepticus

Drug-induced liver injury: Discontinue with jaundice or evidence of significant liver injury

Dose-dependent decreases in serum T3 and T4 (free and total) values reported

Rare cases of pancytopenia, agranulocytosis, and leukopenia have been reported during postmarketing use of eslicarbazepine; consider discontinuation of treatment in patients who develop pancytopenia, agranulocytosis, or leukopenia

Points of recommendation

:Instructions
May take with or without food
May swallow table whole or crush
Discontinuation: Reduce dose gradually and avoid abrupt discontinuation to minimize risk of increased seizure frequency and status epilepticus

:Adverse Effects

Dizziness, Headache, Somnolence, Nausea, Diplopia , Blurred vision, Vomiting, Diarrhea, Fatigue, Ataxia, Balance disorder, Falls, Tremor, Hyponatremia, Asthenia, Gait disturbance, Peripheral edema, Urinary tract infections, Depression, Rash, Insomnia, Dysarthria, Memory disturbance, Nystagmus, Diarrhea and constipation, Abdominal pain, Leukopenia, agranulocytosis, thrombocytopenia, megaloblastic anemia, pancytopenia and Syndrome of inappropriate antidiuretic hormone secretion or SIADH

:Drug Interactions
Contraindicated: artemether/lumefantrine, cariprazine, cobimetinib, dienogest/estradiol valerate, doravirine, elbasvir/grazoprevir, elvitegravir/cobicistat/emtricitabine/tenofovir DF, lonafarnib, lumacaftor/ivacaftor, lumefantrine, lurasidone, naloxegol, ombitasvir/paritaprevir/ritonavir & dasabuvir, oxcarbazepine, panobinostat, praziquantel, regorafenib, rilpivirine, roflumilast, vandetanib
Serious, Use Alternative: abemaciclib, acalabrutinib, apremilast, avanafil, avapritinib, axitinib, bedaquiline, bosutinib, brigatinib, cabazitaxel, cabozantinib, ceritinib, clopidogrel, cobicistat, copanlisib, crizotinib, dabrafenib, deflazacort, dihydroergotamine, dihydroergotamine intranasal, dronedarone, eliglustat, elvitegravir, entrectinib, ergotamine, erythromycin, ethinylestradiol, everolimus, fedratinib, flibanserin, ibrutinib, idelalisib, irinotecan, ivabradine, ivacaftor, ivosidenib, ixazomib, lefamulin, lemborexant, levonorgestrel, lorlatinib, lurbinectedin, macimorelin, macitentan, metoclopramide, midostaurin, naldemedine, neratinib, netupitant/palonosetron, olaparib, osimertinib, palbociclib, pemigatinib, pomalidomide, ponatinib, pretomanid, ranolazine, rimegepant, rolapitant, romidepsin, selumetinib, sildenafil, silodosin, siponimod, sirolimus, sofosbuvir/velpatasvir, sonidegib, tazemetostat, tezacaftor, tolvaptan, trabectedin, ulipristal, valbenazine, vemurafenib, venetoclax, vorapaxar, voxelotor, zanubrutinib

:Contraindications
Hypersensitivity to eslicarbazepine or oxcarbazepine

Pregnancy level

Limited available data with eslicarbazepine acetate use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes

Advise women of reproductive potential taking eslicarbazepine acetate who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control

Breast feeding warning

Eslicarbazepine is present in human milk; effects of eslicarbazepine acetate on the breastfed infant or on milk production are unknown

Related drugs

Oxecarbazepin


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