Indication(s):
Adjunctive treatment of partial-onset seizures.
Pharmacology:
Aptiom is extensively converted to eslicarbazepine, which may be responsible for therapeutic effects in humans. The precise mechanism by which eslicarbazepine exerts anticonvulsant activity is unknown, but is thought to involve inhibition of voltage-gated sodium channels.
Clinical Trials:
The efficacy of Aptiom as adjunctive therapy was established in 3 randomized, double-blind, placebo-controlled trials in adults with epilepsy. Patients enrolled had partial-onset seizures with or without secondary generalization and were not adequately controlled with 1–3 concomitant AEDs.
Studies 1 and 2 compared Aptiom 400mg, 800mg, and 1200mg once daily with placebo. Study 3 compared Aptiom 800mg and 1200mg once daily with placebo. In all trials following an 8-week baseline phase, patients were randomized to a 2-week initial titration phase, and then a subsequent 12-week maintenance phase.
The primary efficacy endpoint was the standardized seizure frequency during the maintenance phase over 28 days. The Aptiom 400mg/day dose was studied in Studies 1 and 2 and did not show significant treatment effect. A statistically significant effect was observed with Aptiom 800mg/day in Studies 1 and 2, and with Aptiom 1200mg/day in all 3 trials. Results in Study 1 showed that the Aptiom 800mg arm had a seizure frequency value of 5.0 (P=0.047) and the Aptiom 1200mg arm had a value of 4.3 (P=0.001) vs. 6.6 with placebo. In Study 2, the Aptiom 800mg arm showed a value of 6.2 (P=0.006) and the Aptiom 1200mg arm had a value of 6.6 (P=0.042) vs. 8.6 with placebo. In Study 3, the Aptiom 1200mg arm had a value of 6.0 (P=0.004) vs. 7.9 with placebo.
Legal Classification:
Rx
Adults:
Initially 400mg once daily; increase to 800mg once daily after one week. Max maintenance dose: 1200mg once daily (initiate only after ≥1 week at 800mg once daily). May initiate at 800mg once daily if need additional seizure reduction and outweighs increased adverse reaction risk. Moderate-to-severe renal impairment (CrCl <50mL/min): initially 200mg once daily; increase to 400mg once daily after 2 weeks. Max maintenance dose of 600mg once daily may be beneficial.
Children:
<18 years: not established.
Warnings/Precautions:
Increased risk of suicidal thinking or behavior; monitor for clinical worsening or unusual changes. Discontinue if serious dermatologic reactions or DRESS/multi-organ hypersensitivity occurs. Measure serum sodium and chloride levels during therapy and esp. if hyponatremia symptoms develop. Monitor for neurological adverse reactions (esp. in elderly). Monitor LFTs at baseline; discontinue if jaundice or evidence of significant liver injury occurs. Severe hepatic impairment: not recommended. Avoid abrupt cessation. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interaction(s)
Do not take as adjunctive therapy with oxcarbazepine. Antagonized by carbamazepine, phenobarbital, phenytoin, and primidone; monitor and adjust dose. May potentiate phenytoin, clobazam, omeprazole. May antagonize simvastatin, rosuvastatin. May decrease effectiveness of oral contraceptives; use additional non-hormonal forms. May affect thyroid function tests. Caution with other drugs known to decrease serum sodium. Monitor INR when given with warfarin.
Adverse Reaction(s)
Dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision, tremor; rare: serious skin reactions (eg, SJS, TEN), DRESS/multi-organ hypersensitivity, anaphylaxis, angioedema, liver injury.
Notes:
To enroll in the North American Antiepileptic Drug Pregnancy Registry call (888) 233-2334.
How Supplied:
Tabs 200mg, 400mg—30; 600mg—60, 90; 800mg—30, 90
LAST UPDATED:
4/24/2014
