Hazard and Precautionary Statements (GHS)

Eslicarbazepine Chemical Properties,Usage,Production

Description

Eslicarbazepine is a third- generation AED sold under the proprietary brand names of Zebinix® (Eisai, Hatfield) in the UK and Aptiom® (Sunovion, Marlborough, MS) in the USA.

Generic formulation

MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):

• The need for continued supply of a particular manufacturer’s product should be based on clinical judgment and consultation with the patient and/ or carer, taking into account factors such as seizure frequency and treatment history.

Indications

Epilepsy: monotherapy and adjunctive therapy of focal seizures.

Recommendations summarized from NICE (2012)
Seizure types: adjunctive (focal seizures).

Dose titration

400 mg od, increased to 800 mg od after 1– 2 weeks (max. 1200 mg od).

Plasma levels monitoring

Plasma level monitoring has a minimal role in the therapeutic use of eslicarbazepine due to the relatively predictable pharmacokinetics of the drug.

Cautions

• Elderly patients.
• Patients with hyponatraemia.
• Patients with prolonged PR interval.

Interactions

With AEDs

• Concomitant administration of eslicarbazepine and carbamazepine or phenytoin can result in a decrease in exposure to the active metabolite of eslicarbazepine, most likely caused by an induction of glucuronidation. therefore, the dose of eslicarbazepine may need to be increased if used concomitantly with carbamazepine.
• Concomitant administration of eslicarbazepine and phenytoin can result in an increase in exposure to phenytoin, most likely caused by an inhibition of CYP2C19.
• Concomitant use of eslicarbazepine with oxcarbazepine is not recommended because this may cause overexposure to the active metabolites.

With other drugs

• Concomitant administration of eslicarbazepine and combined oral contraceptive, simvastatin, rosuvastatin, and warfarin results in a decrease in systemic exposure to levonorgestrel and ethinylestradiol, simvastatin, rosuvastatin, and warfarin, most probably caused by an induction of CYP3A4.
• Based on a structural relationship of eslicarbazepine to tricyclic antidepressants, an interaction between eslicarbazepine and monoamino oxidase inhibitors is theoretically possible.

With alcohol/food

• There are no known specific interactions between alcohol and eslicarbazepine, and there are no specific foods that must be excluded from the diet when taking eslicarbazepine.

Special populations

Hepatic impairment

• No dose adjustment is recommended in patients with mild to moderate hepatic impairment.
• The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment.

Renal impairment

• Dose adjustment (reduce initial dose to 400 mg every other day for 2 weeks, then 400 mg od) is recommended in patients with renal impairment and lower creatinine clearance.

Pregnancy

• There are no data from the use of eslicarbazepine in pregnant women. If women receiving eslicarbazepine become pregnant or plan to become pregnant, the use of eslicarbazepine should be carefully re- evaluated. Minimum effective doses should be given and monotherapy, whenever possible, should be preferred, at least during the first 3 months of pregnancy.
• It is unknown whether eslicarbazepine acetate is excreted in human milk. As a risk to the breastfed child cannot be excluded, breastfeeding should be discontinued during treatment with eslicarbazepine

Behavioural and cognitive effects in patients with epilepsy

For this third-generation agent, clinical experience is still limited, and little is known about its positive and negative psychotropic properties, and their implications for the management of behavioural symptoms in patients with epilepsy.