Prescribing Information

Zebinix (eslicarbazepine acetate)

Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentations: Tablets containing 200 mg or 800 mg eslicarbazepine acetate. Oral suspension containing 50 mg eslicarbazepine acetate per millilitre (50 mg/ml). Indication: Monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy. Adjunctive therapy in adults, adolescents and children aged above 6 years with partial-onset seizures with or without secondary generalisation. Dosage and administration: Oral use. Adults: Starting dose is 400 mg once daily, increased to 800 mg once daily after one or two weeks. Dose may be increased to 1200 mg once daily, based on individual response, or 1600 mg once daily in some monotherapy patients. Elderly >65 years: No dose adjustment required if renal function is not disturbed. Monotherapy dose of 1600 mg is not recommended. Children and adolescents >6 years old: Starting dose is 10 mg/kg/day once daily, increased in weekly or bi-weekly increments of 10 mg/kg/day up to 30 mg/kg/day based on individual response. Maximum dose:1200 mg/day. Children with a body weight ≥ 60 kg: dose as for adults. Renal impairment: Use with caution. Adjust dose according to creatinine clearance (CLCR). Not recommended in severe impairment (CLCR<30 mL/min). Hepatic impairment: No dose adjustment in mild to moderate impairment but use with caution. Not recommended in severe impairment. Contra-Indications: Hypersensitivity to the active substance, other carboxamide derivatives or any excipients. Second or third-degree AV block. Warnings and precautions: Withdraw gradually to minimise the potential of increased seizure frequency. Suicidal Ideation: Monitor patients for signs of suicidal ideation and behaviours. Advise patients (and caregivers) to seek medical advice if these occur. Nervous system: dizziness and somnolence. Cutaneous reactions and hypersensitivity: Rash, urticaria and angioedema. If signs or symptoms of hypersensitivity develop, discontinue immediately. Severe cutaneous adverse reactions (SCARs) which can be life-threatening or fatal have been reported. At time of prescription patients should be advised of signs and symptoms. Monitor closely for skin reactions and these develop, discontinue Zebinix immediately and do not restart at any time. Zebinix oral suspension contains methyl parahydroxybenzoate (E218) which may cause allergic reactions and sulphites which may rarely cause severe hypersensitivity reactions and bronchospasm. HLA-B*1502- in Han Chinese, Thai and other Asian populations: screen for this for allele whenever possible as it has been shown to be strongly associated with the risk of developing Stevens-Johnson syndrome (SJS) when treated with carbamazepine. Screening of other genetically at-risk Asian populations should also be considered. HLA-A*3101- European descent and Japanese populations: Allele has been associated with an increased risk of developing carbamazepine induced cutaneous adverse reactions including SJS, toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS) or less severe acute generalised exanthematous pustulosis (AGEP) and maculopapular rash in patients of European descent and Japanese population. Hyponatraemia: Examine serum sodium levels before and during treatment in patients with pre-existing renal disease or who are treated with medicines which may lead to hyponatraemia.

Determine sodium serum levels if clinical signs of hyponatraemia occur. Discontinue if clinically relevant hyponatraemia develops. PR interval: associated with increase in PR interval. Caution in patients with medical conditions or taking concomitant medicines associated with PR prolongation. May affect ability to drive and use machines. Pregnancy and lactation: No data on use in pregnant women. Animal studies have shown reproductive toxicity. Carefully re-evaluate treatment if women taking Zebinix become pregnant or plan to become pregnant. Unknown if excretion occurs in human breast milk. Patients should not breast feed. Drug interactions: Interaction studies performed in adults only. Eslicarbazepine acetate has an inducing effect on the metabolism of medicinal products mainly eliminated by CYP3A4. The dose of these medicines may need increase when used concomitantly with Zebinix. May have an inducing effect on the metabolism of medicinal products mainly eliminated by UDP- glucuronyl transferases. May take 2 to 3 weeks to reach the new level of enzyme activity when initiating, discontinuing or changing Zebinix dose. Take time delay into account when using with, or just prior to, other medicines that require dose adjustment. Has inhibiting properties with respect to CYP2C19. Prescribers should consult the SPC in relation to all interactions. Oral contraceptives: Interacts with oral contraceptives. Women of childbearing potential must use adequate contraception during treatment with Zebinix, and up to the end of the current menstrual cycle after discontinuation. Warfarin: Monitor INR during the first weeks after initiation or ending concomitant treatment. Undesirable effects: In clinical studies, these were usually mild to moderate in intensity and occurred predominantly during the first weeks of treatment. Very common effects (≥1/10): dizziness, somnolence. Common effects (≥1/100 to <1/10): hyponatraemia, decreased appetite, insomnia, headache, disturbance in attention, tremor, ataxia, balance disorder, diplopia, vision blurred, vertigo, nausea, vomiting, diarrhoea, rash, fatigue, gait disturbance, asthenia, weight increased. This is not a complete list of adverse reactions. Prescribers should consult the SPC in relation to all adverse reactions. Paediatric population: Similar to adults. Agitation and abdominal pain were more common. Most common adverse reactions: in age 6-11 years were diplopia, somnolence, dizziness, convulsion and nausea and age 12-18 years were somnolence, vomiting, diplopia and fatigue. The safety of Zebinix in children aged 6 years and below has not yet been established. Overdose: Symptoms primarily associated with central nervous system and cardiac disorders. There is no known specific antidote. Legal Category: POM. Basic UK NHS cost: Zebinix 200mg tablets: pack of 60 £68.00, Zebinix 800mg tablets: pack of 30 £136.00, Zebinix Oral Suspension 50mg/mL: 200mL bottle £56.67. Marketing authorisation numbers: Zebinix 200mg 60 tablets: PL 21566/0005 EU/1/09/514/022; Zebinix 800mg 30 tablets: PL 21566/0009 EU/1/09/514/017. Zebinix Oral Suspension 50 mg/mL 200mL bottle: PL 21566/0007 EU/1/09/514/024. Marketing authorisation holder: Bial-Portela & Cª., S.A. À Av. da Siderurgia Nacional 4745-457 S. Mamede do Coronado – Portugal.
Date of preparation: May 2021. Job code: UK/ZB/2021/034(1)

ADVERSE EVENTS SHOULD BE REPORTED

Reporting forms and information can be found at www.yellowcard.mhra.gov.uk or in Ireland: www.hpra.ie
Adverse events should also be reported to BIAL on +44 (0) 1753 916 010 (UK) / +353 818 370 074 (ROI) or medical.info.uk_ie@bial.com

UK/ZB/2021/032(1)
Date of preparation: July 2021​