Effect of eslicarbazepine acetate on the pharmacokinetics of digoxin in healthy subjects

Silva, Manuel Vaz da; Costa, Raquel; Soares, Eva; Maia, Joana; Falcão, Amı́lcar; Almeida, Luís; Soares-da-Silva, Patrı́cio

doi:10.1111/j.1472-8206.2009.00691.x

Cited by 24 publications

(7 citation statements)

References 12 publications

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“…A two‐way crossover, randomized, study in 12 healthy subjects did not reveal any interaction of ESL (1,200 mg/day for 8 days) with digoxin (on days 1–2, 0.5 mg/day and on days 3–8, 0.25 mg/day) with no effect on digoxin AUC [GMR (90% CI):96% (90–103%)], and a slight decrease of in digoxin – C max [GMR – (90% CI) 85% (68–107%)] in digoxin C max GMR (90% CI) that appears to have no clinical relevance (Vaz‐da‐Silva et al., 2009).…”

Section: Interactions With Other (Non‐aed) Medicationsmentioning

confidence: 99%

Pharmacokinetics and drug interactions of eslicarbazepine acetate

2012

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SUMMARYEslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life (t 1/2,eff ) of eslicarbazepine was 20-24 h, which is approximately two times longer than its terminal half-life (t 1/2 ). At clinically relevant doses (400-1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral contraceptive and simvastatin.

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Section: Interactions With Other (Non‐aed) Medicationsmentioning

confidence: 99%

Pharmacokinetics and drug interactions of eslicarbazepine acetate

2012

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“…ESL may not cause QT prolongation, but the evaluation of electrocardiogram recordings during clinical trials showed an increase in PR interval in ESL-treated patients, which was highest in the 1200 mg dose group compared with the placebo group. Finally, ESL was associated with very few psychiatric events, and the incidence of rash was low 12,14,16–18,24,29–31,35,40,44,45…”

Section: Resultsmentioning

confidence: 97%

Update on treatment of partial onset epilepsy: role of eslicarbazepine

Rauchenzauner

Luef²

2010

NDT

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Partial epilepsy comprises simple partial seizures, complex partial seizures, and secondarily generalized seizures, and covers more than 60% of patients with epilepsy. Antiepileptic drugs are generally considered to be the major therapeutic intervention for epilepsy but, despite a broad range of commonly used antiepileptic drugs, approximately 30% of adult patients and approximately 25% of children with epilepsy have inadequate seizure control. Eslicarbazepine acetate (ESL) is a novel voltage-gated sodium channel-blocking agent with presumed good safety and efficacy for adjunctive treatment of patients with drug-resistant partial epilepsy. ESL is a prodrug of eslicarbazepine (the active entity responsible for pharmacologic effects), and is rapidly and extensively hydrolyzed during first pass by liver esterases after oral administration. The half-life of eslicarbazepine at steady-state plasma concentrations is 20–24 hours, compatible with once-daily administration. ESL 800 mg and 1200 mg significantly reduces seizure frequency and shows a favorable safety profile in adult patients with drug-resistant partial-onset seizures, as demonstrated in previous Phase II and III trials. In children, ESL showed a clear dose-dependent decrease in seizure frequency with good tolerability. The most commonly reported adverse events associated with ESL are dizziness, somnolence, nausea, diplopia, headache, vomiting, blurred vision, vertigo, and fatigue. In conclusion, these characteristics suggest that ESL might be a valid and well tolerated treatment option for patients with drug-resistant partial-onset epilepsy. The convenience of once-daily dosing and a short, simple titration regimen would be of special interest for children, although conclusive published data are lacking to date. Hence, there is an urgent need to establish the therapeutic value of ESL in this special population in the near future.

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“…• Both, coadministration of ESL 1200 mg once daily and digoxin or ESL 1200 mg and metformin were well tolerated and did not influence pharmacokinetics in healthy subjects [44,45];…”

Section: Drug Profilementioning

confidence: 97%

Eslicarbazepine acetate for partial-onset seizures

Rauchenzauner

Luef

2011

Expert Review of Neurotherapeutics

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Eslicarbazepine acetate (ESL), a new voltage-gated sodium channel blocker that is chemically related to carbamazepine and partially metabolized to oxcarbazepine, has attracted attention as results of previous Phase II and III studies demonstrated and confirmed efficacy and tolerability of ESL 800 and 1200 mg once daily as add-on therapy for adult patients with drug-resistant partial-onset seizures. In children, efficacy data point towards a dose-dependent decrease in seizure frequency and tolerability analyses showed a low incidence of mild drug-related adverse effects at 5 and 15 mg/kg/day. The most frequently reported adverse effects were dizziness, somnolence, headache, diplopia, nausea and vomiting. The convenience of once-daily dosing and a short/simple titration regimen in combination with a comparative efficacy and tolerability profile might promote ESL as a valid alternative to the current adjunctive antiepileptic drug therapy armamentarium for drug-resistant partial seizures in adults. Since clinical trials in children and adolescents on ESL efficacy and safety are ongoing and data already published are far from conclusive, the therapeutic value of ESL in this special population has to be established in the near future.

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Effect of eslicarbazepine acetate on the pharmacokinetics of digoxin in healthy subjects

Cited by 24 publications

References 12 publications

Pharmacokinetics and drug interactions of eslicarbazepine acetate

Pharmacokinetics and drug interactions of eslicarbazepine acetate

Update on treatment of partial onset epilepsy: role of eslicarbazepine

Eslicarbazepine acetate for partial-onset seizures

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