Rationale for Initiation, Continuation and Discontinuation (RICaD) Eslicarbazepine acetate (Zebinix®)

For monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy; or adjunctive therapy in adults, adolescents and children aged above 6 years, with partial- onset seizures with or without secondary generalisation.

This document supports the use and transfer of a treatment initiated by the hospital. It is intended for completion by specialists in order to give Primary Care prescribers a clear indication of the reason for initiating the medication together with suggested criteria for its subsequent continuation or discontinuation. This RICaD should be provided as a supplement to the specialist’s clinical letter.

Patient details GP details Specialist details Name GP Name Dr Specialist PID GP address NI camonfeir m that this patient has been initiated on eslicarbazepine for the reasons shown below

DOB Signature Patient address Date Contact details

Rationale for Choice and Guidance on initiation

 monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in Relevant adults with newly diagnosed epilepsy; Diagnosis:  adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation. Reason why eslicarbazepine Uncontrolled with or intolerant to other antiepileptic drugs has been chosen

Pre-treatment Regular blood test monitoring in adults is not recommended as routine, and should be done only if clinically test results indicated. (NICE CG137)

400 mg once daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, the dose may be increased to 1,200 mg once Adults daily. Some patients on monotherapy regimen may benefit from a dose of 1,600 mg once daily

Elderly (over 65 years No dose adjustment provided that the renal function is not disturbed of age) 1,600 mg once daily is NOT recommended due to lack of data

CLCR >60 ml/min: no dose adjustment required.

Initiation dose CLCR 30-60 ml/min: initial dose of 200 mg (or 5 mg/kg in children above 6 years) once Renal impairment daily or 400 mg (or 10 mg/kg in children above 6 years) every other day for 2 weeks followed by a once daily dose of 400 mg (or 10 mg/kg in children above 6 years). CLCR <30 ml/min: use is not recommended No dose adjustment is needed in patients with mild to moderate hepatic Hepatic impairment impairment. Eslicarbazepine has not been evaluated in severe hepatic impairment Children above 6 years of age Paediatric population The recommended starting dose is 10 mg/kg/day once daily. Dosage should be

Wolverhampton Area Prescribing Committee Page 1 of 3 Eslicarbazepine acetate RICaD July 2018 Review: July 2020

increased in weekly or bi-weekly increments of 10 mg/kg/day up to 30 mg/kg/day, based on individual response. The maximum dose is 1,200 mg once daily Children with a body weight of ≥60 kg Children with a body weight of 60 kg or more should be given the same dose as for adults.

Monitoring Regular blood test monitoring in adults is not recommended as routine, and should be done only if clinically indicated. (NICE CG137)

 Women of child bearing potential must use adequate contraception during treatment with eslicarbazepine, and up to the end of the current menstruation cycle after the treatment has been discontinued  Eslicarbazepine reduces the effect of oral contraceptives. Mechanical methods (e.g. condoms), medroxyprogesterone acetate (Depo Provera) or an IUD are recommended. Contraceptive implants will also have reduced efficacy.  Screening for the HLA-B* 1502 allele in Han Chinese, Thai and other Asian populations should be carried out before starting treatment, if possible.  Eslicarbazepine is contraindicated in patients with hypersensitivity to the active substance or to other carboxamide derivatives (e.g. carbamazepine, oxcarbazepine) or to any of the excipients  Eslicarbazepine is contraindicated in patients with Second or third degree atrioventricular (AV) block  Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic medicinal products in several indications. Therefore, patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatments should be considered. Patients (and caregivers of patients) Special should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. precautions  Eslicarbazepine acetate has been associated with some central nervous system adverse reactions, such as dizziness and somnolence, which could increase the occurrence of accidental injury.  Rash developed as an adverse reaction in 1.2% of total population treated with eslicarbazepine in clinical studies in epileptic patients. If signs or symptoms of hypersensitivity develop, eslicarbazepine acetate must be discontinued.  Hyponatraemia has been reported as an adverse reaction in 1.5% of patients treated with eslicarbazepine. Hyponatraemia is asymptomatic in most cases, however, it may be accompanied by clinical symptoms like worsening of seizures, confusion, decreased consciousness  Prolongations in PR interval have been observed in clinical studies with eslicarbazepine acetate. Caution should be exercised in patients with medical conditions (e.g. low levels of thyroxine, cardiac conduction abnormalities), or when taking concomitant medicinal products known to be associated with PR prolongation.  Caution should be exercised in the treatment of patients with renal impairment and the dose should be adjusted according to creatinine clearance Check the current BNF and SPC for detailed precautions, contraindications and drug interactions.

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Patients should be monitored when changing eslicarbazepine doses as the doses of their other epilepsy medicines may need to be adjusted.

Summary of potential pharmacokinetic interactions between eslicarbazepine and other medications Effect of eslicarbazepine on other Effect of other drugs on drugs eslicarbazepine Phenytoin ↑↑ ↓ Phenobarbital ↑↑ ↓? Additional Topiramate ↓? ↔ information Lamotrigine ↓? ↔ Carbamazepine ↓? ↓ Valproate ↔ ↔ Levetiracetam ↔ ↔ Warfarin ↓? ↔ Ethinylestradiol ↓ ? Tolbutamide ↑ ?

Suggested Criteria for Continuation or Discontinuation

Assessment of Efficacy Frequency of At least annually. review Location Outpatient clinic or GP practice.

Method (what Regular blood test monitoring in adults is not recommended as routine, and should be done only if clinically tests are indicated. (NICE CG137) required)

Continuation Effective Seizure Control & improved Quality of life and compliance confirmed. Criteria

 Patient Choice  Not responding to eslicarbazepine Discontinuation  Not tolerating eslicarbazepine Criteria

If eslicarbazepine is to be discontinued it is recommended to withdraw it gradually to minimise the potential of increased seizure frequency

Follow up action

Wolverhampton Area Prescribing Committee Page 3 of 3 Eslicarbazepine acetate RICaD July 2018 Review: July 2020